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Cancer treatment in the Arab-Islamic medicine: Integration of tradition with modern experimental trails

  • Arab American University (AAUP) & Al-Qasemi Academic College


Cancer is a cohort of disorders that involves transformation, dysregulation of apoptosis, uncontrolled cell proliferation, invasion, angiogenesis and metastasis. Extensive research during the last five decades has revealed much about the biology of cancer. Drugs used to treat most cancers are those that can block cell cycle, cell signaling, including growth factor signaling; inflammation, angiogenesis and others. Strikingly, herbal plant extracts and based drug, including those attributed to the Islamic civilization were reported to mediate their effects by modulating several of these recently identified therapeutic pathways. Ibn Sina (Avicenna) and al Razi (Rhazes) described most types of cancers known at their time and suggested several treatments based on their believe that cancer is a result of excess of burned black bile in the affected tissue. Therefore, they recommended evacuation of the organ from black bile by excessive vomiting and laxatives and using cold medications and food. The Andalusian scholar Alzahrawi was the first to conduct classic removal of breast cancer and to invent more than 200 surgical equipments. He recognized that cancer can be treated surgically only in its early stages when complete removal is possible. The focus of this review is to elucidate the Arab-Islamic anticancer therapies suggested by the most famous Arab and Muslim scholars notably, Avicenna (980-1037), Rhazes (965-1015), Al Zahrawi (936-1013) and Ibn al Nafis (1218-1288). Furthermore, cancer classification, causes, pathogenesis and prevention; surgical removal of tumors; herbal remedies; dietary modifications; and spiritual treatments are also highlighted.
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
Cancer treatment in the Arab-Islamic medicine: Integration of
tradition with modern experimental trails
Hilal Zaid and Bashar Saad
Cancer is a cohort of disorders that involves transformation, dysregulation of
apoptosis, uncontrolled cell proliferation, invasion, angiogenesis and metastasis.
Extensive research during the last five decades has revealed much about the biology
of cancer. Drugs used to treat most cancers are those that can block cell cycle, cell
signaling, including growth factor signaling; inflammation, angiogenesis and others.
Strikingly, herbal plant extracts and based drug, including those attributed to the
Islamic civilization were reported to mediate their effects by modulating several of
these recently identified therapeutic pathways. Ibn Sina (Avicenna) and al Razi
(Rhazes) described most types of cancers known at their time and suggested several
treatments based on their believe that cancer is a result of excess of burned black
bile in the affected tissue. Therefore, they recommended evacuation of the organ
from black bile by excessive vomiting and laxatives and using cold medications and
food. The Andalusian scholar Alzahrawi was the first to conduct classic removal of
breast cancer and to invent more than 200 surgical equipments. He recognized that
cancer can be treated surgically only in its early stages when complete removal is
possible. The focus of this review is to elucidate the Arab-Islamic anticancer
therapies suggested by the most famous Arab and Muslim scholars notably,
Avicenna (980-1037), Rhazes (965-1015), Al Zahrawi (936-1013) and Ibn al Nafis
(1218-1288). Furthermore, cancer classification, causes, pathogenesis and
prevention; surgical removal of tumors; herbal remedies; dietary modifications; and
spiritual treatments are also highlighted.
Key words: Cancer, medicinal plants, Arab herbal medicine, Avicenna, garlic,
black seeds.
Hilal Zaid and Bashar Saad
14 )2010(،
Cancer is a leading cause of death worldwide. It strikes more than one third of the
worlds population and it’s the cause of more than 20% of all deaths (Toni et al.,
2010). Cancer is a cohort of diseases characterized by uncontrolled cell
proliferation and ability to invade other tissues through direct cell migration or
through the blood and lymph systems. More than 100 different types of cancer are
known, usually are named by the organ/tissue or type of cell in which they start.
For example, cancer that begins in the colon is called colon cancer. A tumor is an
extra mass of cells with abnormalities in their DNA. Tumors may be benign (not
cancer), or malignant (cancer). Among many others, the causes of cancer might be
tobacco smoke, infection, chemicals, radiation, environmental factors, and
unhealthy diet (Figure 1).
In addition to uncontrolled cell proliferation, some cancer cells have the ability to
invade neighboring tissues and may also affect other distant tissues/organs. As
recognized by Avicenna and Alzahrawi, if the tumor is diagnosed at an early stage,
it can be successfully treated. Advanced tumors are treated usually by
chemotherapy and although these drugs are effective, they are associated with
severe adverse events and drug resistance (Baguley, 2010; Yan and Wajapeyee,
2010). Traditional Arab-Islamic herbal-based medicines might be promising
candidates for new cancer therapeutics with low toxicity and minimal side effects
(Saad et al., 2006; Saad et al., 2008b; Said et al., 2008).
The origins of Arab-Islamic medicine can be traced back to the time of the Prophet
Mohammad, Peace Be Upon Him (PBUH) as a significant number of Hadiths
concerning medicine are attributed to him. Several Sahaba were successfully
treated of certain diseases by following the medical advice of the Prophet
Mohammad (PBUH). The most famous of the Prophet Hadiths on medicine are:
"There is no disease that Allah has created, except that He also has created its
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
treatment", "Make use of medical treatment, for Allah has not made a disease
without appointing a remedy for it, with the exception of one disease, agedness.",
"Allah has sent down both the disease and the cure, and He has appointed a cure
for every disease, so treat yourselves medically", "The one who sent down the
disease sent down the remedy", "For every disease, Allah has given a cure".
Moreover, some verses in the Holy Quran also emphasis that every disease has a
remedy. For instance: "Say: It is for those who believe, a guide and a healing
[Fussilat 41:44] And We send down of the Quran that which is a healing and a
mercy to those who believe” [al-Israa’ 17:82]. The unlimited Muslims belief in the
Prophet (PBUH) and that there is a cure for every disease encouraged early
Muslims scholars to engage in botanical and other natural products, chemical and
biomedical research to seek out a cure for every disease known to them.
During the Golden Arab-Islamic Age (7
to 14
century), many of the famous
Arab and Muslim physicians studied cancer and applied various medicines and
surgical methods. For instance, Ibn Sina (980-1037), known in the west as
Avicenna, was the most influential of all Islamic philosopher-scientists, suggested
When cancer starts, it may be possible to keep it as it is, so that it will not
increase and keep it non-ulcerated. It may happen sometimes that the stating
cancer may be cured. But when it is advanced, verily will not”. Hence, it is
worthwhile looking back in the history to the views of old masters in the Arab
medicine. It is appropriate to introduce first the history of the Arab and Islamic
medicine for the reader who is not familiar with it.
The history of the Arab and Islamic medicine is divided into two phases: Greek-to-
Arab phase and Arab-Muslim phase. The first phase started in the eighth century
when the Arab-Islamic Empire ruled about two-thirds of the world. This
magnificent spread allowed them to get and translate Greek scientific and
philosophical manuscripts as well as Indian and Persian scripts. Hunayn Ibn-Is'haq
(809-873), translated a large number of scientific and medical manuscripts in
Hilal Zaid and Bashar Saad
14 )2010(،
Greek (including philosophical works by Galen, Plato, Aristotle, Euclid and
Archimedes) into Arabic during the glory years of the Abbasid Caliphate (756-
945). Some of the Greek physicians, especially Galen (129-199) were acquainted
with tumors. It is believed that Galen was the first to deal with tumors, including
cancer, in a systematic way. He adopted Hippocrates' (470-370 BC) basic theory of
cancer as an excess of black bile. In the golden Islamic-Arab time, classic Greek
texts including those of Galen, were translated into Arabic, and influenced
physicians in the Arab-Islamic world. Disease, including cancer, was viewed in
terms of the four Greek bodily fluids (Humors)—blood, phlegm, yellow bile, and
black bile.
During the second phase, by 850, most of the philosophical and scientific works of
Aristotle; much of Plato and the Pythagorean School; the major works of Greek
astronomy, mathematics and medicine as well as the works of Hippocrates and
Galen, were all rendered into Arabic. For the next 700 years, Arabic became the
most important scientific language of the world and the repository of much of the
wisdom and the sciences of antiquity (Hitti, 1970; Saad et al., 2008b). During this
golden age of the Arab-Islamic civilization, numerous scientific and medical
innovations were introduced. Notably, the discovering of the immune system, the
introduction of microbiological science, the introduction of scientific methods to
medicine including animal tests, clinical trials, quantification and the separation of
medicine from pharmacological science. For instance, the earliest known medical
experiment was carried out by Rhazes (865 - 915). In his ‘Comprehensive Book of
Medicine’, Rhazes described clinical cases of his own experience and provided
very useful recordings of various diseases. Avicenna's wrote almost 450 treatises
on a wide range of subjects, of which around 240 have survived and 40 of them
concentrate in medicine. Perhaps The Canon of Medicine is the most
comprehensive and the best-known amongst them. It was a standard medical text in
Europe and the Islamic world up until the 18
century. Avicenna and many other
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
Arab and Muslim scientists introduced numerous new ideas, upgraded the
knowledge about herbs and their potential medical efficacy and safety (Said et al.,
2010). Here we aim to shed a light on the Arab and Islamic cancer diagnosis,
herbal treatment and nowadays herbal-based treatment research.
Cancer diagnostic and treatment by the Arab and Islamic medicine: The most
effective way for illness prevention according to Arab-Islamic belief is healthy
diet. Prophet Mohammad (PBUH) said “food is the source of illness; however the
diet program is the source of health”. The Holy Quran contains a verse which
sums up all medicine: "Eat and drink but do not be prodigal, He does not like/love
the wasters” (al-Ar'af 7:31).
Avicenna also had discussed the diet effect on cancer progression. In regard of
cancer prevention he said that “As to preventing its (cancer) progress, it can be
achieved by …" improving the diet and reinforcing the involved organ by the
known effective medications" It is well known nowadays that several chemicals are
carcinogenic [figure1 and (Volanis et al., 2010)] and that obesity is a cause of
various diseases including cancer (Brown and Simpson, 2010; Fuemmeler et al.,
It is worth however to emphasize that Rhazes, Avicenna and Abulcasis identified
several cancer types, including eye, nasal, tongue, stomach (gastric), liver, the
urinary system, kidney, testis, and breast cancer, as well as spleen and nerve tumor.
For instance, kidney's cancer was mentioned clearly, for the first time, by Al
Zahrawi (Abulcasis 936 - 1013) who had distinguished between kidney acute
inflammation and kidney cancer. Both; Rhazes and Avicenna described cancer as a
tumor which is extremely difficult disease to treat.
Rhazes, Abulcasis and Avicenna realized that a cure is most likely if the cancer
was identified at its earliest stage (Avi Senna, 1037; Rhazes, 925). The first goal of
a treatment strategy should be to halt the cancerous growth. They suggested
Hilal Zaid and Bashar Saad
14 )2010(،
surgical removal if the tumor was small and accessible, and not close to major
organs (Figure 2). In his Canon, Avicenna described four ways to treat cancer: (a)
total arrest (but it is difficult); (b) preventing its progress; (c) preventing ulceration;
(d) treating of ulceration. He empathized that medications should not be of much
strength, since strong medications increase cancer evil. In addition, “one should
avoid irritant medications. And for this, good medications are: pure minerals like
washed pure tutty mixed with oils like rose oil and the oil of yellow gillyflower
mixed with it” (Avi Senna, 1037). Avicenna also described one of the very early
surgical treatments for cancer, in his Canon, he noted: “the excision should be
radical and that all diseased tissue should be removed, which included the use of
amputation or the removal of veins running in the direction of the tumor … so that
nothing of these will be left. He also recommended the use of cauterization for
the area being treated if necessary”. Other citation by Avicenna “….and it was told
by one of the predecessors that a physician had excised a cancerous breast
radically then cancer developed in the other breast. My opinion is that the second
breast might have been on its way to cancerization (a dormant cancer) which fits
this case and it is possible to be a spread of the material (cancerous from the first
breast) and this is more evident (opinion)…. Avicenna also attempted the earliest
known treatments for cancer. One method he discovered was the "Hindiba"
(chicorium intybus), an herbal compound drug which Ibn al-Baitar later identified
as having anticancer properties and which could also treat other tumors and
neoplastic disorders (AlTurkimany, 1993; Hitti, 1970; Ibn AlBitar, 1874; Saad et
al., 2008b).
Prevention and treatment of cancer in the Greco-Arab and Islamic herbal
medicine: Herbal-based preparations have been used worldwide for thousands of
years to treat various forms of diseases including cancer. Currently,
chemoprevention represents a novel approach for controlling cancer, which involve
the use of specific natural products or synthetic chemical agents to reverse,
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
suppress or prevent pre-malignancy before the development of invasive cancer.
Several natural products, such as, grains, nuts, fruits, vegetables and medicinal
plants confer protective effects against wide range of cancers. Since diet has an
important role in the body health, dietary chemoprevention received attention in the
Arab-Islamic treatment of diseases including cancer. The Holy Quran states several
plants as well as animal products among the foods Muslims can enjoy and benefit
from their nutritional and health values. Among some of the foods mentioned in the
Holy Quran and Hadith by the Prophet (PBUH) are grapes, citrus, melon, squash,
figs dates, honey, olive oil, and black seeds. The Prophet (PBUH) mentioned figs
and then stated, "If I had to mention a fruit that descended from paradise I would
say this is it because the paradisiacal fruits do not have from these fruits
for they prevent hemorrhoids, prevent piles and help gout." Figs are a top source of
fiber, as well as potassium and vitamin B6. Fiber results in bulkier stools, which
lessen the incidence of constipation, hemorrhoids and colon cancer. Melon was
among one of the fruits most often eaten by the Prophet (PBUH). In fact, melon is
one of the best recommendations for health the Prophet has given us. Melon is one
of the few fruits and vegetables rich in vitamin C, Beta-Carotene, and potassium.
He recommended the use of olive oil, by a statement "Eat olive oil and massage it
over your bodies since it is a holy (Mubarak) tree". Black seeds were regarded as a
medicine for that cures all types of diseases. The Prophet once stated, "The black
seed can heal every disease, except death". Dates are mentioned in twenty places in
the Quran. Prophet (PBUH) is reported to have said: "if anyone of you is fasting, let
him break his fast with dates. In case he does not have them, then with water.
Verily water is a purifier".
Avicenna had mentioned also that "it (cancer) can be reached by controlling the
material, improving the diet and reinforcing the involved organ by the known
effective medicines, and by using mineral smears like those containing millstone
dust and whet-stone dust and from smears taken from a mixture between the stone
Hilal Zaid and Bashar Saad
14 )2010(،
pounder for aromatics and black head stone moisturized with rose oil and
coriander water….".
Due to place limitations we will focus on six widely used herbal products, namely,
garlic, onion, black seeds, pomegranate, grapes and Palestinian arum. Other
commonly used medicinal plants and wild edible plants are described in (Zaid et
al., 2010).
Garlic and onion (Allium sativum L. and Allium cepa): The Prophet Mohammad
said although onion and garlic have a bad smell, they are cures for 70 different
illnesses that cannot be cured by any other means”.
Onion (Allium cepa) and garlic
(Allium sativa) are closely-related vegetables that belong to the Allium class of
bulb-shaped plants, which also includes chives, leeks, and scallions. Garlic is used
for flavoring in cooking and is unique because of its high sulfur content. In
addition to sulfur, garlic also contains arginine, oligosaccharides, flavonoids and
selenium, all of which may be beneficial to health (Milner, 1996). In fact onion and
garlic are used in the treatment and prevention of a number of diseases, including
cancer, heart disease, obesity, hypercholesterolemia, diabetes type 2 and
hypertension. Scientific research on garlic started in the 19
century with the work
of Louis Pasteur who in 1858 first noted antibacterial properties of garlic (Pasteur,
The association between consumption of Allium vegetables and risk for cancer has
been first assessed in several epidemiologic studies, to show the protective effect of
garlic and onion against cancer. For instance, death (attributed to stomach cancer)
was 10 fold higher in a high risk area where the garlic consumption is less than
1g/day compare to the low risk area (20 g/day) (Mei et al., 1982; Takezaki et al.,
1999). Similar studies in Netherlands had also attributed the low risk for colorectal,
breast, and lung cancers to onion and garlic consumption (Dorant et al., 1996).
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
Findings from a study on the association between garlic consumption and colon
cancer risk, shows clearly that women who consumed the highest amounts of garlic
had a 50 percent lower risk of cancer of the distal colon compared with women
who had the lowest level of garlic consumption (Steinmetz et al., 1994). Moreover,
breast cancer risk was reduced in women consuming greater amounts of fiber
garlic, and onions (Challier et al., 1998). Garlic and onion consumption was also
associated with reduced risk of esophageal and stomach cancers, with greater risk
reductions seen for higher levels of consumption (Gao et al., 1999), an
approximately 30-50 percent reduction in prostate cancer risk (Colli and Amling,
2009; Hsing et al., 2002), pancreatic cancer (Chan et al., 2005) and other distinct
cancer types (Kim and Kwon, 2009). The amount of garlic consumed on the above
studies varied from 2 up to 20 g daily. It is worthy to note that although garlic has
been used safely in cooking, excessive consumption can cause some side effects, in
addition to strong breath and body odors (Boon and Wong, 2004). The World
Health Organization (WHO) guidelines for general health promotion for adults is a
daily dose of 2 to 5 g of fresh garlic (approximately one clove), 0.4 to 1.2 g of
dried garlic powder, 2 to 5 mg of garlic oil, 300 to 1,000 mg of garlic extract, or
other formulations that are equal to 2 to 5 mg of allicin (the active compound in
garlic). The protective effect of Allium vegetables against tumor proliferation and
angiogenesis is attributed mainly to its organosulfur compounds especially allicin
and diallyl disulfide (Arnault and Auger, 2006). Those active compounds are able
to block the formation of cancer-causing substances (Shenoy and Choughuley,
1992), halt the activation of cancer-causing substances (Milner, 2001; Powolny and
Singh, 2008), enhance DNA repair (L'Vova G and Zasukhina, 2002), reduce cell
proliferation, or induce apoptosis -programmed cell death (Figure 1 and (Arnault
and Auger, 2006; Malki et al., 2009)).
Onion and garlic organosulfur compounds protective effect against carcinogenesis
was also evaluated in animal models and in-vitro. When administrated to mice 2-4
Hilal Zaid and Bashar Saad
14 )2010(،
days prior to carcinogen challenge, those compounds inhibited pulmonary adenoma
formation (Sparnins et al., 1988). Intravenous administration of the garlic active
compound (diallyl trisulfide) significantly retarded the growth of orthotopically
transplanted hepatoma in BALB/c nude mice (Zhang et al., 2007). Those
compounds had also halted the proliferation of cells from various cancer cell lines,
including human, lung, skin and colon tumor cell lines, human neuroblastoma
cells, human and murine melanoma cells, and human prostatic carcinoma cells
(Sakamoto et al., 1997; Sundaram and Milner, 1996; Takeyama et al., 1993; Welch
et al., 1992) .
Black seeds (Nigella sativa): Nigella sativa is one the most revered medicinal
seeds in history. In civilizations around the world, herbal spice Nigella Sativa
referred to as Habbat-el-barakah (literally seeds of blessing in Arabic), Kalonji
(Hindi), Kezah (Hebrew), Sijah Daneh (Persian) and in English called Black
Caraway. The famous Greek physician Dioscorides (40-90 AC) used black cumin
seeds to treat headaches and toothaches. Nigella sativa seeds and oil extracts has
been used widely for centuries to treat interruptions in the respiratory system,
stomach, kidney and liver function, circulatory, the immune system as well as
cancer. In Islam, it is regarded as one of the greatest forms of healing medicine
available (Zohary and Hopf, 2007). The prophet Mohammad (PBUH) stated, "The
black seed can heal every disease, except death". Avicenna refers to black seed in
his ‘Canon of Medicine’, as the seed that stimulates the body's energy and helps
recovery from fatigue and dispiritedness. In the Unani Tibb system of medicine,
seeds are regarded as a valuable remedy for a number of diseases. The seed's oil
has been used to treat skin conditions such as eczema and boils and to treat cold
The modern research confers that Nigella sativa seeds ethanol extract possess
antitumor activity in mice tumor primary cells (Musa et al., 2004). Nigella sativa
seeds extracts contains amino acids, proteins, carbohydrates, alkaloids, saponins,
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
fixed and volatile oils, and many others. Among the volatile oil, Thymoquinone
(TQ) is the main active compound (Ghosheh et al., 1999). TQ affects multiple
targets, including suppression of, anti apoptotic genes expression and thus
enhances apoptosis induction (Kaseb et al., 2007). Moreover, TQ inhibited cell
proliferation of many types of cancer cell lines, including breast adenocarcinoma,
ovarian adenocarcinoma (Shoieb et al., 2003), human pancreatic adenocarcinoma,
colorectal cancer (Gali-Muhtasib et al., 2004a), uterine sarcoma (Worthen et al.,
1998), human osteosarcoma (Roepke et al., 2007), neoplastic keratinocytes (Gali-
Muhtasib et al., 2004b) and fibrosarcoma, lung carcinoma (Kaseb et al., 2007).
More recently, it was reported that TQ blocks tumor angiogenesis in vivo (mouse
model) and in vitro (human umbilical vein endothelial cell -HUVEC) (Yi et al.,
Pomegranate (Punica granatum): The pomegranate has long been used in
traditional Greco-Arab and Islamic medicine to treat a variety of ailments,
including sort throat, inflammation and rheumatism. The fruit is also used for
treating bladder disturbances, strengthening gums and soothing mouth ulcers.
Pomegranates feature prominently in all religions Islam, Judaism, Christianity,
Buddhism and Zoroastrianism. According to the Quran, pomegranates grow in the
gardens of paradise. Among the small number of fruits and vegetables mentioned
in the Quran, (including date, olive, grape, banana, fig, cucumber, garlic, lentil and
onion) pomegranate is mentioned three times, indicating its significance in
Muslims life
The pomegranate fruit has been used for centuries in ancient cultures for medicinal
purposes. For a long time, the fruit has been widely consumed fresh and, more
recently, in beverage form as juice. Pomegranate is known as an anti- oxidant and
is used to treat several diseases including cancer, inflammation, cardiovascular
disease, diabetes, bacterial infections and antibiotic resistance, as well as ultraviolet
Hilal Zaid and Bashar Saad
14 )2010(،
radiation-induced skin damage (Jurenka, 2008; Lansky and Newman, 2007).
However, most of the research groups has focused on its antioxidant, anti-
inflammatory and anticarcinogenic properties.
It is now well documented that pomegranate is effective in treating prostate cancer.
In in-vitro experiments, Pomegranate fruit extract decrease proliferation and
induced apoptosis of DU-145 prostate cancer cells and suppressed invasive
potential of PC-3 cells. These effects may be associated with plant based anti-
inflammatory effects (Lansky et al., 2005; Malik and Mukhtar, 2006). Moreover,
Mukhtar and his colleges reported that oral administration of Pomegranate fruit
extract resulted in significant inhibition of tumor growth in prostate tumor model
mice (Malik and Mukhtar, 2006). Pomegranate fruit extract was also effective in
inhibition of lung tumorigenesis in mice (Khan et al., 2007), suggesting that
consuming pomegranates could potentially help reduce the growth and spread of
prostate and lung cancer cells or even prevent cancer from developing.
Pomegranate juice was also effective in inhibition of inflammatory cell signaling in
colon cancer (Adams et al., 2006).
The pomegranate anticancer activities is not limited to its juice, but also the peel
and seeds oil have been shown to be effective against tumor cell proliferation, cell
cycle, invasion and angiogenesis (Lansky and Newman, 2007). Concomitant,
pomegranate seed oil suppressed colon carcinogenesis in mice (induced by
azoxymethane) (Kohno et al., 2004). The anti-carcinogenic effects of the different
parts and compounds of the pomegranate, is describes elsewhere (Lansky and
Newman, 2007; Syed et al., 2007).
Grapes (Vitis vinifera): Grapes exerts several health benefits including but not
limited to anti-inflammatory and anti-cancer effects, prevent lipid oxidation and
platelet aggregation. The main active compound in grapes is polyphenol
compound; Resveratrol. Resveratrol is believed to decrease circulating LDL (low-
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
density lipoprotein) cholesterol levels and thus reduce cardiovascular disease risk.
(Ramprasath and Jones, 2010). Grapes and many other fruits and vegetables are
rich in antioxidant compounds called flavonoids. They're among the plant
chemicals that have also shown potential against heart disease. Flavanoids as well
as the whole blake grape (including seeds) were shown to inhibit key inzymes in
the tumurgenic cell, thereby inducing apoptosis and or stoping their growth (Durak
et al., 2005; Jo et al., 2006). In Rats, grape seeds extracts (proanthocyanidins)
reduced the ulcerative colitis progress which is known to significantly increased
risk of colorecl cancer (Li et al., 2008).
Palestinian Arum (Arum palaestinum): Arum is edible plant and is widely used
in cocking. According to a general survey conducted on 2008, Palestinian Arum is
one of the most known as anti cancerous (especially colon cancer) plants in
Palestine (Ali-Shtayeh et al., 2008). Moreover, Arum Plasetenum is also effective
against internal bacterial infections, poisoning and circulatory system. However,
the action mechanism of Palestinian Arum awaits further studies.
The wisdom of the past led to the discovery of chemopreventive drugs- The past
medical literature is a valuable source of information which has the potential
suggestions to the contemporary scientists. Several studies have revealed that
natural products exhibit an extensive spectrum of biological activities such as,
stimulation of the immune system, antibacterial, antiviral, anti-hepatotoxic, anti-
ulcer, anti-inflammatory, antioxidant, anti-mutagenic, and anti-cancer effects (Al-
Johar et al., 2008; Boon and Wong, 2004; Cragg and Newman, 2005; Saad et al.,
2008a; Saad et al., 2008b). A variety of grains, cereals, nuts, soy products, olives,
beverages such as tea and coffee, and spices including turmeric, garlic, ginger,
black pepper, cumin and caraway confer a protective effect against cancer (Al-
Johar et al., 2008; Boon and Wong, 2004; Challier et al., 1998; Chan et al., 2005;
Hilal Zaid and Bashar Saad
14 )2010(،
Clifford and Digiovanni, 2010). Several studies have also documented the
relationship between decreased cancer risk and high consumption of vegetables,
including cabbage, cauliflower, broccoli, brussels sprout, tomatoes, and fruits such
as, apples and grapes (Chan et al., 2005; Cragg and Newman, 2005; Saad et al.,
2008b; Vainio and Weiderpass, 2006). In addition, a number of medicinal plants
and herbs have also been reported to reduce the risk of cancer in multiple sites
[Figure 1 and (Kroll et al., 2007; Park and Pezzuto, 2002)].
Traditional herbal medicines provide a remarkable source for new drug
development. Indeed, about 50% of the modern drugs are herbal based (Harvey,
2008). Since natural based products are inherently better tolerated in the body
compared to synthetic chemicals and have higher chance to be approved as new
drugs, searching for and purification of natural drug candidates is imperative. In the
case of anti cancer drugs, various drugs are derived from plant sources including
but not limited to paclitaxel (taxol), vinblastine, capsaicin, vincristine, the
camptothecin derivatives, topotecan, irinotecan and etoposide [table 1 and (Butler
and Newman, 2008; Cragg et al., 2009; Cragg and Newman, 2005; Saklani and
Kutty, 2008)]. Many commonly used anti-cancer herbs possess chemopreventive
effects within there diverse pharmacological properties. Since cancer evolves over
a long period of time, agents that inhibit or retard one or more of its stages could
affect the overall course of the disease. Certain micronutrients (like Oleuropein and
Diallyl sulfide compounds found in olives and garlic respectively) possess potent
cancer-preventive abilities.
The current emphasis should be laid on identification the action mechanism of the
plant-based drugs on cancer prevention and treatment and combining this remedy
with modern developments in medicine. For instance, combination of the Baby
Birth plant (Gypsophila paniculata L.) with the sapoins based chemotherapy
increase the sensitivity of the tumurgenic cells for the chemotherapy drugs
treatments several ten folds in vito an in vivo animal models (Weng et al., 2009).
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
Concluding remarks
There is no doubt that Avicenna, Rhazes and Al-Zahrawi influenced the field of
cancer medicine and the principles laid down by them were recognized as authentic
in medical science, especially surgery, and these continued to influence the medical
world for five centuries. Despite the rapidly increasing understanding of the
molecular and cellular processes, such as gene and protein expression, apoptosis,
angiogenesis, signal transduction involved in carcinogenesis, the morbidity of this
epidemiologic disease is still rising. In fact, cancer epidemiology is just increasing
every day and it has revealed that certain cancers are more common among people
of some cultures than others. Cancers of the lung, colon, prostate and breast are
very common in Western countries; they are not as prevalent in Eastern countries.
Yet, the prevalence of cancer in the current Arab-Islamic countries is in an increase
mode. The best ways for cancer treatment is preventing its causes (Figure 1) and
diagnose it at earlier stages as state earlier. Yet we still need to continue searching
for the most effective anti-cancerous drug as the Prophet (PBUH) stated: “The one
who sent down the disease sent down the remedy”. Several drugs are used to treat
and prevent the development of tumorgenesis. However, these treatments are not
always effective and usually are accompanied with side effects. Alternative
treatment, e.g. herbal plants might be a potential safe candidate for use and
treatment of several diseases including cancer. Several studies have been
conducted in vivo and in vitro to evaluate herbal plants efficacy on carcinogenesis
Hilal Zaid and Bashar Saad
14 )2010(،
Table1. Selected natural derived chemicals used in divers diseases remedy
including cancer.
Drug and Source Activity Mechanism
Betulinic acid from the
bark of several species
of plants, principally the
white birch (Betula
Inhibitor of human
melanoma, anti-retroviral,
anti-malarial, and anti-
Antiproliferative and
Camptothecin from
Happy Tree
Treats lung, breast, ovarian,
and colorectal cancer
Inhibits the DNA enzyme
topoisomerase I leading to
Capsaicin from Pepper
Anti- carcinogenic and anti-
tumor promotion effects.
Relieve the pain of
peripheral neuropathy,
itching and inflammation
Interacts with sensory
neurons, binds to a receptor
called the vanilloid receptor
subtype1 (VR1)
Curcumin from
Turmeric (Curcuma
Multiple myeloma,
pancreatic cancer,
myelodysplastic syndromes,
colon cancer, psoriasis, and
Alzheimer's disease
Antitumor, antioxidant,
antiarthritic, anti-amyloid,
anti-ischemic and anti-
Etoposide from
Lung cancer, testicular
cancer, lymphoma, non-
lymphocytic leukemia
Inhibits the enzyme
topoisomerase II, causing
DNA strands to break
Irinotecan from Happy
Tree (Camptotheca
Colon and rectum cancer Inhibits the DNA enzyme
topoisomerase-I, causes
DNA damage and apoptosis
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
Drug and Source Activity Mechanism
Lapachol from Trumpet
tree (Tabebuia sp.)
Anti-several types of cancer.
Nowdays is rarly used due to
its toxic side effects
It is a derivative of
naphthoquinone, related to
vitamin K.
Paclitaxel (Taxol) from
Pacific yew (Taxus
Treating ovary and breast
Interferes with the growth
of cancer cells and slows
their growth and spread in
the body
Podophyllotoxin from
mayapple (Podophyllum
Anti- lung cancer,
lymphomas, and genital
Arrest the cell cycle by
inhibition of tubulin
Topotecan from Happy
Tree (Camptotheca
Treating ovarian or lung
cancer that do not respond
well to other types of cancer
Inhibits the DNA enzyme
topoisomerase I, leading to
DNA damage and apoptosis
Vinblastine from
Madagascar periwinkle
plant (Catharanthus)
Treat some types of
lymphoma, Hodgkin’s
disease, testicular cancer,
breast cancer,
choriocarcinoma and others
Interferes with the growth
of cancer cells, slows their
growth and spread in the
Vincristine from
Madagascar Periwinkle
(Catharanthus roseus)
Treats leukemia, diabetes,
malaria, and Hodgkin's
It binds tubulin, thereby
inhibiting the assembly of
microtubules thus prevent
separation of chromosomes
during mitosis
Epothilone from
Sorangium cellulosum
Currently undergoing
clinical development for
treatment of various cancers
Inhibition of microtubule
function therefore stops
cells from properly dividing
Hilal Zaid and Bashar Saad
14 )2010(،
Figure1. Summary of the potential Cancer causes and the possible cellular targets
of the herbal anti cancer derived drugs and extracts.
Cancer treatment in the Arab-Islamic medicine: :
Integration of tradition with modern e xperimental trails
14 )2010(،
Figure 2. Some of the 200 surgical instruments introduced by AlZahrawi.
Hilal Zaid and Bashar Saad
14 )2010(،
The authors would like to acknowledge Mr. Bahaa Hadiah for preparing figure 1,
the USDA-Agricultural Research Service (ARS) and the Ministry of Absorption
for providing their financial support.
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14 )2010(،
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... Thymoquinone, Amino acids, proteins, alkaloids, saponins, carbohydrates, volatile oil Antitumor, immuno enhancing, anti inflammatory [23,92] 33 ...
... Tannin, ellagic acid, punicic acid,flavonoids,anthocyanidin,estr ogenic flavonols, flavones anti inflammatory,Anticarcinogenic, anti oxidant, cardioprotective, anti diabetic, [92] 34 Neem Azadirachta indica Limonoids (Azadirachtin) anti inflammatory,Antiulcer, anti oxidant, hepatoprotective, anti cancer, antimetastatic [92] 35 ...
... Tannin, ellagic acid, punicic acid,flavonoids,anthocyanidin,estr ogenic flavonols, flavones anti inflammatory,Anticarcinogenic, anti oxidant, cardioprotective, anti diabetic, [92] 34 Neem Azadirachta indica Limonoids (Azadirachtin) anti inflammatory,Antiulcer, anti oxidant, hepatoprotective, anti cancer, antimetastatic [92] 35 ...
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Cervical cancer is the most common gynecologic malignancy worldwide. It is the leading cause of death among females, accounts for 8.5% deaths per year. Human papilloma virus is the major risk factor. In classical Unani text, cervical cancer (sartan al- rahim) is caused by warame har or warame sulb of rahim and also due to dominance of khilte sawda (black bile), which is formed due to ehtiraq (detonation) of khilte safra (yellow bile). Clinical features are excessive tiredness, loss of appetite, foul smelling discharge per vaginum, pelvic pain, urinary symptoms, etc. Treatment options in conventional medicine include radical hysterectomy with pelvic lymph nodes dissection and concurrent chemo or radio therapy which have their own side effects like nausea, vomiting, loss of appetite and hair, early bruising and bleeding, anemia, renal problems, etc. Nowadays in spite of a number of interventions available, large number of patients suffers from poor prognosis. Therefore, the effort for finding new anticancer agents as an alternative with better efficacy and minimum side effects has been continued. Hence, there is a need for newer treatment which is to be safe, cost effective, easily available and free from side effects. The aim of this review paper is to provide evidence based analysis to Unani drugs having anti cancerous, activities in the treatment of cervical cancer. Moreover, this review article is focused to discuss how unani drugs and various food items act as anticancerous from scientific and medical point of view and how they are considered to be safe, effective and less expensive with virtually no side effects in the management of cervical cancer. Keywords: sartan al- rahim, cervical cancer, anticancerous, unani medicine
... Daucus carrota Linn (carrot) Apiaceae Antioxidant effect for prevention of tumor [147] 78. Camptotheca acuminata Cornaceae Inhibits the DNA enzyme topoisomerase I, leading to DNA damage and apoptosis [200] 79. Catharanthus Apocynaceae Treats leukemia, It binds tubulin, thereby inhibiting the assembly of microtubules thus prevent separation ofchromosomes during mitosis. ...
... Catharanthus Apocynaceae Treats leukemia, It binds tubulin, thereby inhibiting the assembly of microtubules thus prevent separation ofchromosomes during mitosis. [200] 80. Strychnos nux-vomica Loganiaceae Cell cycle analysis showed G2/M phase arrest and apoptosis [103] Adel et al. ...
... In fact, the earliest hominid cancer described to date corresponds to a 1.7 million-year-old osteosarcoma case characterized in South Africa [79]. Interestingly, similarly to bacterial infections, cancer treatments were also based on the "humor theory" through the mid-19th century, with progressive incorporation of improved surgical techniques [80,81]. It was not until the 1890s that X-rays were used as the first form of radiotherapy [82], around 1940 for the beginning of chemotherapy [83], after 1970 for the use of antibodies [84], and much more recently for the use of protocols targeting the immune checkpoints [85], bringing immunotherapy to the first line of currently available anticancer therapies. ...
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Cancer is predominantly considered as an environmental disease caused by genetic or epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or intrinsic (e.g., metabolic, immune or genetic deficiencies). Over-exposure to antibiotics, which is favored by unregulated access as well as inappropriate prescriptions by physicians, is known to have led to serious health problems such as the rise of antibiotic resistance, in particular in poorly developed countries. In this review, the attention is focused on evaluating the effects of antibiotic exposure on cancer risk and on the outcome of cancer therapeutic protocols, either directly acting as extrinsic promoters, or indirectly, through interactions with the human gut microbiota. The preponderant evidence derived from information reported over the last 10 years confirms that antibiotic exposure tends to increase cancer risk and, unfortunately, that it reduces the efficacy of various forms of cancer therapy (e.g., chemo-, radio-, and immunotherapy alone or in combination). Alternatives to the current patterns of antibiotic use, such as introducing new antibiotics, bacteriophages or enzybiotics, and implementing dysbiosis-reducing microbiota modulatory strategies in oncology, are discussed. The information is in the end considered from the perspective of the most recent findings on the tumor-specific and intracellular location of the tumor microbiota, and of the most recent theories proposed to explain cancer etiology on the notion of regression of the eukaryotic cells and systems to stages characterized for a lack of coordination among their components of prokaryotic origin, which is promoted by injuries caused by environmental insults.
... Methods that included the use of certain diets, use of herbs and drugs that had less poisonous materials were also used that Islamic physicians, who could be considered pioneers in chemotherapy. 3 Perhaps today's science owes itself to the thousands of years of Iranian and Islamic civilization of these scholars, in particular of Bouali Sinai and his commentators. The science of the world of cancer has not changed significantly. ...
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Background: One of the great physicians in Iran who had expertise in medicine, surgery, and pharmacy was Sadid al-Din Kazeroni. He was a 14th century physician. No information is available on his birth and death – only “Al-Mughni”, a book, has been left to make him famous in surgical and medical knowledge. Methods: We used desk and historical research methods in this research, with a historical approach. This commonly used research method in human sciences was used to criticize and study the birthplace and works of Sadid al-Din Kazeroni. Results and Conclusion: Sadid al-Din Kazeroni discussed the exact issues in the field of anatomy, surgery, and gynecology. He was fluent in pharmacology. In his pharmacology book, for the first time, he named drugs considered necessary before and after surgery. In this study, we reviewed the biography and introduction of the works and reviewed “Al-Mughni”, a book on breast cancer.
... Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough and unexplained weight loss, (American cancer society, 2017). Drugs used to treat most cancers are those that can block cell cycle, cell signalling, including growth factor signalling; inflammation, angiogenesis and others, (Saad, B., et al, 2010). Strikingly, herbal plant extracts and based drugs, including those attributed to the Islamic civilization were reported to ...
... Cancer is a malignant form of disease resulting from uncontrolled cell division. The resulting proliferating cells have the ability to invade other tissues through direct cell migration or through the vascular system [1]. There are more than 200 types of cancer that take the name of the organ, tissue, or cell in which they originate [2]. ...
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Background: Cancer is a common malignant disease that affects a large number of individuals worldwide , including Iraq with a high prevalence and mortality rate. Aim: Investigation for cancers in one of Iraq cities. Methods: A total of 12,000 specimens from patients suspected to have cancer in a Karbala city in Iraq between 2008 and 2015 was histopathologically examined to diagnose various types of cancer diseases. The prevalence, incidence rate, and age-specific rate (ASP) were determined for 838 confirmed positive cases (320 males and 518 females). Results: In males, high prevalence and incidence rate were observed for bladder, gastro-oesophageal (GOC), colorectal, lymphoma, and prostate cancers, while in females, breast, thyroid, lymphoma, colorectal, bladder, and gastro-oesophageal cancers were highest. The prevalence of all types of cancer was higher in females than in males during almost all the survey periods. ASR was observed higher in the older age groups for most patients with cancer. Some cancers were also prevalent at younger ages (≤30 years). Conclusion: The high prevalence and incidence rate of many types of cancer in Karbala were of concern, especially for older age groups. In this survey, bladder cancer in males and breast cancer
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Cervical ectopy is one of the commonest gynecological conditions seen in OPD’s, about 80-85% of women suffer from cervical ectopy during their life time. Many a times, it is an accidental finding in an asymptomatic woman coming for routine gynecological examination. Although it is a benign lesion, but may predispose to complications like infertility, cervical intraepithelial neoplasm, risk of various sexually transmitted infections like C. trachomatis, N. gonorrhoea, human papilloma virus, human immunodeficiency virus, cytomegalovirus and shows malignant changes as it progresses. Ectopy occurs when the columnar epithelium lining the endocervix, extends onto the ectocervix. As the disease takes 10-20 years to progress from pre invasive to invasive disease, preventive measures such as screening and treatment modalities should be adopted. Early diagnosis of cervical ectopy is important for its effective management and for prevention of its long-term sequel. The treatment option available in conventional medicine includes surgical procedure either electro or, cryocautery, but have their own complications. Hence, this treatment is limited due to its complications and contraindications and need for safer alternate therapy. In Unani system of medicine, various formulations are available as treatment of quruhal rahim, which have been recommended to be used locally in the form of humool for immediate healing of wound, exhibiting the properties of anti-inflammatory (muhallile warm), desiccant (mujaffif), wound healing (mundamile qurooh), sedative (musakkin), antiseptic (dafa’e ta’ffun) etc. This review article gives a detailed description of cervical ectopy as mentioned in classical Unani text including its etiopathogenesis, clinical presentation and principles of treatment as well as evidence-based Unani medicine.
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Cancer is one of the most dreaded diseases of the 20th century and spreading further with continuance and increasing incidence in 21st century and additionally is set to become a major cause of morbidity and mortality in the coming decades in every region of the world. Moreover, cancer is a complex disease involving numerous tempospatial changes in cell physiology, which ultimately lead to malignant tumors. Abnormal cell growth (neoplasia) invasion of surrounding tissues and distant organs is the primary cause of morbidity and mortality for most cancer patients. It is a fatal disease caused mainly by environmental factors that mutate genes encoding critical cell-regulatory proteins. The resultant aberrant cell behavior leads to expansive masses of abnormal cells that destroy surrounding normal tissue and can spread to vital organs resulting in disseminated disease. The cancer-causing agents (carcinogens) can be present in food and water, in the air, and in chemicals and sunlight that people are exposed to. In this chapter we summarize the basic knowledge's in cancer definition, history, etiology, diagnosis, classifications and epidemiology.
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Fruits are sources of various essential nutrients those are vital for health. Having a diet rich in fruits as part of an overall healthy diet may reduce risk of some chronic diseases. However, the main objectives of this study to collect all verses on Qur'anic Fruit Plant Species (QFPS),then discover miracle on their mention in the Holy Qur'an, and discussion of their Folk Medicinal Importance (FMI)in the light of Holy Qur'an, Prophetic traditions and Modern Medical Experiments(MME) in order to show the signs of the Creator. The QFPS are described in this study according to their botanical name, Qur‟anic name, name mentioned in the Prophetic traditions, Arabic name, English name, nature and flavor, basic constituents and medicinal use with caution. Consequently, this study has found seven distinct fruit plant species in the Holy Qur‟an. The QFPS are: Phoenix dactylifera L., (Date palm), VitisviniferaL.,(Grapes),Oleaeuropea L.,(Olive), Punicagranatum L., (Pomegranate), Zizyphusmauritiana Lam.(Jujube),Musa acuminate(Banana) and Ficuscarica L., (Fig). In addition, this study has discovered two Qur'anic Miracles: firstly, the arrangement of fruit plant species mentioned in the Holy Qur'an according to their importance. Secondly, number of mention for fruit plant species in the Holy Qur'an according to their importance. The study concludes that the folk medicine and the modern medicine have been complementing each other in order to promote humans health and comfort.
Traditionally, herbs have been the immediate answer to human ailments in the pursuit of relief. The traditional claims surrounding the use of herbs to manage or treat various maladies have gained significant popularity throughout time. A common disease that requires urgent attention with regard to the development of novel therapeutic agents is cancer. In 2015, cancer accounted for more than 8.8 million deaths and was listed as the second top cause of mortality behind cardiovascular disorders. It is projected that by 2030, 21.7 million new cases of cancer will emerge resulting in around 13 million deaths due to an aging and growing population. Accordingly, a panoply of herbs have been attested to be used by various cultures around the globe in traditional systems of medicine against cancer. Even today, herbs remain an integral part of various cultures and traditions globally. A plethora of herbs are employed in the management of cancer and other ailments in traditional African, Ayurvedic, Arabic & Islamic, Chinese and Mexican medicine and have shown potent anticancer properties when assayed in vitro and in vivo. Hence, the validated therapeutic claims of herbs guarantee their innovative and sustainable use in an attempt to open avenues in anticancer extracts and or drug development.
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Islamic medicine, Arabic medicine, Arab-Islamic medicine, or Greco-Arab and Islamic medicine refers to medicine developed in the Golden Age of the Arab-Islamic civilization, which extended from Spain in the west to Central Asia and India in the east. In temporal terms it covered a period of roughly nine centuries, from the middle of the seventh to the end of the fifteenth century. Medicine was a central part of this medieval civilization. Famous Arab and Muslim physicians, e.g., Rhazes, Avicenna, Al Zahrawi, Ibn al Nafis studied and developed treatments regimes for cancer as well as most known diseases at that time. They described most types of cancers which were known at that time and suggested several therapies. This review is an eye-bird view on the ancient Arab-Greco and Islamic cancer diagnosis, herbal treatment and nowadays herbal treatment research.
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Effects of ethanol extract of Nigella sativa L. on the growth of Ehrlich ascites tumor (EAT), mitotic index, labeling index and on the life span of tumor bear- ing mice were studied. The results from treated animals showed a decrease in viable cell count, an increase in the life span of EAT bearing mice and an increase in the glutathione peroxidation of heart tissue. Cytological stud- ies have revealed a reduction in the mitosis and DNA synthesis. Treatment with the N. sativa extract also resulted in improvements in the morphological features of tumor cells, along with a reduction in intracytoplasmic vacuoles, the appearance of cell membrane blebbing and the staining intensity. The results of the present study suggest that the ethanol extract of Nigella sativa seeds can generate antioxidants, possess antitumor activity, and ameliorate and prolong the life span of mice bearing EAT.
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For more than 50 yr, natural products have served us well in combating infectious bacteria and fungi. During the 20th century, microbial and plant secondary metabolites helped to double our life span, reduced pain and suffering, and revolutionized medicine. The increased development of resistance to older antibacterial, antifungal, and antitumor drugs has been challenged by (1) newly discovered antibiotics (e.g., candins, epothilones); (2) new semisynthetic versions of old antibiotics (e.g., ketolides, glycylcyclines); (3) older underutilized antibiotics (e.g., teicoplainin); and (4) new derivatives of previously undeveloped narrow-spectrum antibiotics (e.g., streptogramins). In addition, many antibiotics are used commercially, or are potentially useful in medicine for purposes other than their antimicrobial action. They are used as antitumor agents, enzyme inhibitors including powerful hypocholesterolemic agents, immunosuppressive agents, antimigraine agents, and so on. A number of these products were first discovered as antibiotics that failed in their development as such, or as mycotoxins.
This book, which contains 99 chapters, focuses on the growing body of knowledge on the role of various dietary plants in reducing disease. Most of the expert reviews define and support the actions of bioflavonoids, antioxidants and similar materials that are part of dietary vegetables, dietary supplements and nutraceuticals. The book's chapters have various general groupings. Some herbal remedies are being developed based upon historic and cultural uses of certain plants and their constituents in disease prevention and health promotion. Discussions of Japanese, African, Korean and South American plants and their extracts help understanding of their potential roles in health as well as historical evidence for their usefulness. Since the goal of this book is to get experts to explore the ways nutraceutical supplements or foods and herbal medicines prevent disease and cancer or promote health, a major section focuses on many plants and health promotion. These include health concerns such as glucose lowering, bone mineral changes, cramps, cognitive function, osteoarthritis, sleep, skin health, weight reduction, eye protection and many others. The conclusions and recommendations from the various chapters will provide a basis for change as well as application of new extracts and botanicals in preventing cancers and health promotion.
We have recently shown that thymoquinone (TQ) is an antineoplastic drug that induces p53-dependent apoptosis in human colon cancer cells. This study evaluated the antiproliferative and pro-apoptotic effects of TQ in two human osteosarcoma cell lines with different p53 mutation status. TQ decreased cell survival dose-dependently and, more significantly, in p53-null MG63 cells (IC(50) = 17 muM) than in p53-mutant MNNG/HOS cells (IC(50) = 38 muM). Cell viability was reduced more selectively in MG63 tumor cells than in normal human osteoblasts. Flow cytometric analysis showed that TQ induced a much greater increase in the PreG(1) (apoptotic) cell population, but no cell cycle arrest in MG63. G(2)/M arrest in MNNG/HOS cells was associated with p21(WAF1) upregulation. Using three DNA damage assays, TQ was confirmed to result in a significantly greater extent of apoptosis in p53 null MG63 cells. Although the Bax/Bcl-2 ratios were not differentially modulated in both cell lines, the mitochondrial pathway appeared to be involved in TQ-induced apoptosis in MG63 by showing the cleavage of caspases-9 and -3. Oxidative stress and mitochondrial O(2)(*-) generation in isolated rat mitochondria were enhanced by TQ as measured by the dose-dependent reduction in aconitase enzyme activity and Amplex Red oxidation respectively. TQ-induced oxidative damage, reflected by an increase in gamma-H2AX foci and increased protein expression levels of gamma-H2AX and the DNA repair enzyme, NBS1, was more pronounced in MNNG/HOS than in MG63. We suggest that the resistance of MNNG/HOS cells to drug-induced apoptosis is caused by the up-regulation of p21(WAF1) by the mutant p53 (transcriptional activity was shown by p53 siRNA treatment) which induces cell cycle arrest and allows to repair DNA damage. Collectively, these findings show that TQ induces p53-independent apoptosis in human osteosarcoma cells. As the loss of p53 function is frequently observed in osteosarcoma patients, our data suggest the potential clinical usefulness of TQ for the treatment of these malignancies.
Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, etoposide, and paclitaxel (Taxol®). Several promising new agents are in clinical development based on selective activity against cancer-related molecular targets, including flavopiridol and Combretastatin A4 phosphate. Recently, plants have yielded several agents showing anti-AIDS activity, and one of these, (+)-calanolide A, is in clinical development.