Sulforaphane in broccoli: The green chemoprevention!! Role in cancer prevention and therapy

Abstract

Isothicyanates present in cruciferous vegetables are known to exhibit chemoprevention by various mechanisms. Presently, there is growing evidence that a phytochemical compound known as sulforaphane in these green leafy vegetables is found to be effective in preventing and treating various cancers such as prostate cancer, breast cancer, colon cancer, skin, urinary bladder and oral cancers. This component is naturally present in the broccoli sprouts, kale, cabbage, cauliflower and garden cress and is available as a
commercial supplementary pill called Broccoli extract. Availability of many bioactive substances such as vitamins, polyphenols, sulfides, glucosinolates and antioxidants makes broccoli consumption important in daily diet regularly. Researchers have named it as “Green chemoprevention.” It is easily affordable and more cost‑effective than the traditional chemopreventive drugs. Results from the epidemiological and experimental
studies have emphasized the role of sulforophane as a complementary or alternative chemopreventive agent.

Full text

© 2020 Journal of Oral and Maxillofacial Pathology | Published by Wolters Kluwer - Medknow
Sulforaphane in broccoli: The green chemoprevention!! Role
in cancer prevention and therapy
D. B. Nandini1, Roopa S. Rao2, B. S. Deepak3, Praveen B. Reddy4
Departments of 1Oral Pathology and Microbiology, 3Conservave Denstry and 4Oral and Maxillofacial Surgery, Dental College, Regional
Instute of Medical Sciences, Imphal, Manipur, 2Department of Oral Pathology and Microbiology, M. S. Ramaiah Dental College,
Bengaluru, Karnataka, India
Review Article
INTRODUCTION
The value of cruciferous vegetables in cancer prevention
is being evaluated widely in the recent years. Fahey et al. in
1997 were the rst to introduce the anticarcinogenic property
of Broccoli sprouts (BSp).[1] Ever since, numerous studies
have shown that young broccoli and its sprouts provide
glucosinolates which have a preventive role in different primary
cancers as well as second tumors which are usually fatal.[2]
Broccoli contains many active biochemical substances
such as carotenoids, Vitamin C and glucosinates.
One such compound is sulforaphane (SFN)
(1‑isothiocyanato‑4‑[methylsulfinyl] butane), which
is derived from a precursor compound known as
glucoraphanin (GPN).[3] Conversion of GPN to SFN
occurs while cutting or chewing broccoli, which exposes the
GPN to the action of the endogenous myrosinase enzyme.
GPN is stable than SFN. GPN is several times more in
sprouts compared to the mature whole heads. In order to
exert physiologic activity, glucosinolates must be converted
to their bioactive form, known as isothiocyanates, by the
heat‑labile enzyme myrosinase.[4] However, this enzyme is
destroyed on cooking or even steaming or blanching for
Isothicyanates present in cruciferous vegetables are known to exhibit chemoprevention by various
mechanisms. Presently, there is growing evidence that a phytochemical compound known as sulforaphane
in these green leafy vegetables is found to be effective in preventing and treating various cancers such
as prostate cancer, breast cancer, colon cancer, skin, urinary bladder and oral cancers. This component is
naturally present in the broccoli sprouts, kale, cabbage, cauliflower and garden cress and is available as a
commercial supplementary pill called Broccoli extract. Availability of many bioactive substances such as
vitamins, polyphenols, sulfides, glucosinolates and antioxidants makes broccoli consumption important in
daily diet regularly. Researchers have named it as “Green chemoprevention.” It is easily affordable and more
cost-effective than the traditional chemopreventive drugs. Results from the epidemiological and experimental
studies have emphasized the role of sulforophane as a complementary or alternative chemopreventive agent.
Keywords: Adjuvant therapy, anticarcinogenic, antioxidant, antitumor, apoptosis, benefits, broccoli, cell
cycle, chemoprevention, effects, glucosinates, isothiocyanates, nutraceuticals myrosinase, sulforaphane
Abstract
Address for correspondence: Dr. D. B. Nandini, Department of Oral Pathology and Microbiology, Dental College, Regional Instute of Medical Sciences,
Imphal, Manipur, India.
E‑mail: nanni29@redimail.com
Submied: 22‑Apr‑2019, Revised: 06‑Sep‑2019, Accepted: 05‑Mar‑2020, Published: 09‑Sep‑2020
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How to cite this article: Nandini DB, Rao RS, Deepak BS, Reddy PB.
Sulforaphane in broccoli: The green chemoprevention!! Role in cancer
prevention and therapy. J Oral Maxillofac Pathol 2020;24:405.
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Nandini, et al.: Sulforaphane in broccoli
Journal of Oral and Maxillofacial Pathology | Volume 24 | Issue 2 | May-August 2020
more than a minute. It is further believed that boiling the
broccoli as well as thawing it below −85°C will spoil its
anticancer properties.[5]
SFN is one of the powerful anticarcinogenic substances
which work by increasing the levels of enzymes in
the liver, which counteract the carcinogenic effects of
chemicals in the food and environment. SFN is linked to
a sugar molecule through a sulfur band which needs to
be broken to release it. Then, a sulfur‑grabbing protein
will remove the exposed sulfur on SFN and inactivate
it. The myrosinase enzyme in the broccoli breaks this
bond. When broccoli is cut or chopped, the myrosinase
enzyme hydrolyzes SFN to form isothiocyanates.[6] SFN
production may reduce due to inactivation of myrosinase
enzyme. Isothiocyanate formation not only depends on
myrosinase but also on epithiospecier protein which helps
in the conversion of hydrolysis products to nitriles at the
expense of isothiocyanates. This protein is temperature
dependent and is known to get destroyed when broccoli
is heated at 60°C–70°C for 5–10 min. In such a condition,
the formation of SFN increases by 3–7 times.[7]
Raw or freshly harvested broccoli should be used whenever
possible. A delay of 10 days might result in loss of GPN
by nearly 80%.[8] Glucosinolates leak out in water while
boiling as they are water soluble. Hence, mild steaming
and microwaving may retain maximum SFN rather than
boiling.[6]
Unlike raw sprouts, many commercially available
supplements do not contain myrosinase, and this cannot
be encapsulated because it is active only when it is fresh.[5]
Consumption of broccoli along with a food ingredient
consisting of myrosinase enzyme provides more amount
of SFN. Mustard seed powder, daikon radish, wasabis,
arugula or coleslaws are some myrosinase‑rich food.
Some myrosinase enzyme is synthesized by the intestinal
bacteria which may not be seen in persons with imbalanced
ora. Myrosinase produced by the microorganisms in the
intestine further acts on the ingested glucosinolates which
have escaped the endogenous myrosinase in the plant.
However, mammalian cells lack this enzyme.[9] Iberin and
erucin are other compounds found in lesser amount in
broccoli extracts, which show similar cancer‑protective
property as SFN.[10]
BIOAVAILABILITY
Once SFN is ingested, it is primarily absorbed in jejunum
and enters circulation by passive diffusion.[11] SFN binds to
thiols of plasma proteins and crosses the plasma membrane
to enter the cells where it reacts with glutathione to form
conjugates which are expelled by the transporter protein
and metabolized to mercapturic acid. These metabolites are
transported to kidney where they are eliminated through
urine. It is observed that the urinary levels correlate with the
dietary consumption and serve as biomarkers.[12,13] SFN is
rapidly absorbed, reaching peak concentration after 1–3 h.
Levels are back to baseline within 72 h. The bioavailability is
said to be 74%. SFN tissue concentration varies depending
on the end organ. For example, SFN concentration in
the skin is less compared to those in plasma due to low
perfusion. Thus, dosage required may be more. Three doses
of 50–200 µmol daily are well tolerated.[14,15]
The amount of SFN varies in different plants of same
species and even in specic parts of the same plant. It also
depends on the cultivation, climate and other agronomic
factors.[11] Broccoli sprouts are said to be 20–50 times more
effective in chemoprevention than the mature heads. First,
sprouts contain more amount of GPN, a potent Phase 2
enzyme inducer and second, they cause less potential toxicity
due to minimal content of indole and b‑hydroxyalkenyl
glucosinolates.[16] Sulforadex or broccomax is a commercially
available synthetic form of SFN.[8]
Presence of myrosinase enzyme, epithiospecier protein,
and preparation of SFN are some other factors which
alter the bioavailability and pharmacokinetics of SFN. The
metabolites of SFN are removed through urine rapidly,
thereby enhancing the elimination of harmful carcinogens.
This process may, however, depend on individual genetic
variation in metabolism and excretion. Cooking methods
using less water such as steaming or microwaving also
increase the bioavailability of SFN. However, boiling,
microwaving at high power (>750 W) and steaming at
high temperature reduce the amount of SFN levels by
inactivating myrosinase enzyme.[16,17]
ROLE OF SULFORAPHANE IN VARIOUS
CANCERS AND EPIGENETIC ALTERATIONS
SFN has numerous cancer‑preventive properties [Table 1].
SFN role has been described in brief and requires a separate
extensive review by itself as there are numerous studies. It
promotes programmed cell death/apoptosis, induces cell
cycle arrest, inhibits angiogenesis, reduces inammation,
alters susceptibility to carcinogens, reduces invasion and
metastasis and exhibits antioxidant and anti‑inammatory
properties.[18] Evidence also suggests that SFN may target
the epigenetic alterations observed in specic cancers,
reversing aberrant changes in gene transcription through
mechanisms of histone deacetylase inhibition, global
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demethylation and microRNA modulation.[19] The role of
cruciferous vegetables in altering genetic expressions via
epigenetic modulation is being widely explored.
Carcinogenesis and cancer progression involve the genetic
and epigenetic changes in genome leading to transcriptional
dysregulation. Epigenetic alterations cause inhibition of the
tumor suppressor genes and promotion of the oncogenes,
leading to cancer development. Epigenetic mechanisms
include posttranslation histone modifications, DNA
global hypomethylation, noncoding RNAs and chromatin
remodeling. Genetic mutations are not reversible, but
epigenetic alterations are potentially reversible, making
them attractive targets for cancer chemoprevention.[19‑21]
The role of SFN in epigenetic modulation has been widely
explored in various cancers. SFN may be involved directly
or indirectly in effective upregulation of transcriptional
activity of certain genes and restoring the epigenetic
alterations. SFN and broccoli sprouts are considered as an
“epigenetics diet” and have shown to modify the epigenetic
pathways by targeting the histone deacetylases (HDAC)
and DNA methyltransferases (DNMT), thereby altering
the gene transcription and expression in cancer. SFN and
sprouts seem to alter the mitochondrial function and reduce
the lipid peroxidation. SFN could reverse the aberrant
epigenetic markers.[22]
Meeran et al. rst observed the signicant inhibition
of DNMT1 and DNMT3a expression by SFN in a
dose‑dependent manner in human breast cancer cells (MCF‑7
and MDA‑MB‑231 cell lines), and to a lesser extent in normal
MCF10A cells. SFN caused signicant downregulation of
human telomerase reverse transcriptase (hTERT) in breast
cancer cells, leading to apoptosis of cancer cells.[23]
Li et al. observed that SFN is a potent HDAC inhibitor,
which suppresses the hTERT, thereby causing the
reactivation of estrogen receptors (ERs) in the ER‑negative
breast cancer cells via epigenetic modulation. Maternal
and early postnatal intake of SFN and broccoli sprouts
was found to be benecial in preventing breast cancer at a
Table 1: Anticancer effects of sulforaphane
Anticancer effects Action of SFN
Induction of cell cycle arrest (S and G2/M) Increases cyclin 2, chk 2, p21
Inhibits cyclin B1, cdk1, cdc25B, cdc2
Reduction in cell proliferation Inhibits Phase 1 enzymes such as the CYP p450 family
Induces Phase 2 enzymes
Induction in apoptosis SFN induces pro‑apoptotic pathway and inhibits anti‑apoptotic pathways, Induces mitochondrial
apoptotic pathway
Increases Bax, induces p21 and p53
Activates Caspases 3, 7, 8 and 9
Reduces Bcl‑2 and Bcl‑XL
Inactivates PARP, decreases HIF1A and β‑catenin
Causes tubulin modulation, induces reactive oxygen species
Causes autophagy in cancer cells
Inhibition of tumor invasion, angiogenesis and
anti‑inflammatory effect
Inhibits NF‑κB pathway, activates Nrf‑2
Regulates MAPK
Inhibits TNF‑α, NLRP3, IL‑1β, IL‑18, IFN‑γ, IL6, IL‑17, IL‑23 and IL‑12, TGF‑β/Smad
Increases IL‑10, IL‑4, Arg1 and YM‑1 (R)
Inhibits NO, iNOS and COX‑2, silences Th17/Th1
Inhibits MMP‑9, LDH and PGE2
ROS, free radicals
Inhibits VEGF, Akt, EGF, CSF
Epigenetic modulation and altered gene
expression through histone deacetylase inhibition,
global demethylation and microRNA modulation
The Keap1/Nrf2 antioxidant pathway modulation
Histone acetyltransferase inhibition ‑ HDAC1, 2, 3 and 4 inhibition, decreases miR‑21 and hTERT
and inhibits DNMT 1 and 3A
Challenges pro‑oncogenic epigenetic pattern
Antimicrobial effects Increases human β defensins 2
Antioxidant effects
Reduction of susceptibility to carcinogens
Induction of the Keap1/Nrf2/ARE pathway related with antioxidant genes and detoxifying
enzymes, such as glutathione S‑transferases
Inhibits Phase 1 enzymes CYP1A1, A2, B1, CYP2B2, CYP3A4
Induces Phase 2 enzymes NQO1, GSTA1, HO ‑1, thereby reducing oxidative stress and DNA damage
Clears DNA‑damaging chemicals, reducing the toxicity on normal cells
SFN: Sulforaphane, PARP: Poly (ADP‑ribose) polymerase, HIF1A: Hypoxia‑inducible factor 1A, NF‑κB: Nuclear factor‑kappa B, Nrf‑2: Nuclear factor
erythroid‑2‑related factor 2, MAPK: Mitogen‑activated protein kinase, TNF‑α: Tumor necrosis factor‑alpha, IL: Interleukin, IFN‑γ: Interferon‑gamma,
TGF‑β: Transforming growth factor‑β, NO: Nitric oxide, iNOS: Inducible NO synthase, COX: Cyclooxygenase, MMP: Matrix metalloproteinase,
LDH: Lactate dehydrogenase, PGE2: Prostaglandin E2, ROS: Reactive oxygen species, VEGF: Vascular endothelial growth factor, EGF: Epidermal
growth factor, CSF: Colony stimulating factor, HDAC: Histone deacetylases, miR: MicroRNA, hTERT: Human telomerase reverse transcriptase,
DNMT: DNA methyltransferases, CYP: Cytochrome P450, NQO: Nitroquinoline‑1‑oxide, GSTA: Glutathione‑s‑transferase, NLRP3: Nucleotide‑
binding domain (NOD)‑like receptor protein 3, YM: A macrophage protein, a novel mammalian lectin
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later life by altering the tumor‑related gene expressions of
TERT, c‑Myc, p16 and p53 as observed by the authors.[24,25]
Atwell et al. have reviewed various preclinical and clinical
studies demonstrating the epigenetic alterations of SFN
in breast and prostate cancer and the role of SFN in the
regulation of cell cycle, apoptosis, inammation, antioxidant
defense and cancer cell signaling and their relationships
with epigenetic mechanism.[20] Kaufman‑Szymczyk et al.
suggested that SFN downregulates histone deacetylase
activity and subsequent alterations in gene promoter
methylation indirectly.[21]
Inhibition of hTERT in MCF‑7 and MDA‑MB‑231 breast
cancer cells and reduction in DNMT1 and DNMT3a by SFN
treatment were observed. SFN caused CpG demethylation
of hTERT. SFN treatment showed chromatin remodeling
with increase in chromatin markers such as H3K9ac and
acetyl‑H4 and decrease in H3K9me3 and H3K27me3 in
hTERT promoter. These changes resulted in the death of
breast cancer cells.[26] SFN caused downregulation of cyclin
D1, CDK4 and pRB and alterations in the levels of DNMT
and HDAC that resulted in the apoptosis of cancer cells.
SFN reduced DNMT expression and repressed methylation
silenced cyclin D2 expression in prostate cancer.[27]
Researchers found that SFN could affect a histone
methylation and could alter gene expression. SUV39H1, an
enzyme in prostate cancer cells, is affected by the exposure
to SFN, thereby suggesting this enzyme as a therapeutic
target. SFN has been proved effective in treating
advanced cancers as well as preventing the metastasis in
combination with the existing conventional therapies. It
helps in re‑expression of tumor suppressor genes, thereby
causing selective killing of cancer cells and reducing cancer
progression. Clinical human trials to prove the beneciary
effects of SFN are widely explored.[28]
SFN targets apoptosis at different steps, including
downregulation of anti‑apoptotic factors Bcl‑2 and
Bcl‑XL, upregulation of proapoptotic Bax, proteolytic
activation of caspase‑3 and degradation and/or cleavage
of poly(ADP‑ribose) polymerase.[29]
SFN induced apoptosis of the human leukemic cells KG1a
and K562 in a dose‑ and time‑dependent manner through
upregulation of Bax and Caspase‑3 and downregulation of
Bcl‑2. SFN exhibited anticancer effects on acute myeloid
leukemic cells as observed by Wang et al.[30]
SF was shown to modulate STAT3 in cancer cells and
prevent ultraviolet (UV) light‑induced skin cancer and
melanoma.[15] SFN causes epigenetic reactivation of Nrf2,
thereby downstreaming target genes HO‑1, NAD(P)
H:Quinone oxidoreductase 1 (NQO1) and UGT1A1 in a
mouse skin tumor model.[24]
SFN could increase mRNA and protein expressions of
Nrf2, and it downstreams target gene NQO1 by reducing
DNMT1 and DNMT3a. SFN also upregulates HDACs
1, 4, 5 and 7 and increases the level of active chromatin
marker acetyl‑histone 3(Ac‑H3) during tumorigenesis in vivo
(using TRAMP mice) and in vitro (using TRAMP C1 cells).
SFN thus downstreams antioxidative stress pathway partly
via epigenetic modications, and via expression of the
Nrf2 gene.[31]
SFN is a potent inducer of detoxication pathways by
promoting antioxidant glutathione. It leads to the inhibition
of Phase 1 enzymes such as cytochrome 450 that are
responsible for cell proliferation and tumor growth.
SFN induces Phase 2 enzymes by various mechanisms,
thereby removing the DNA‑damaging chemicals. Nuclear
factor erythroid‑2 (NF‑E2‑)‑related factor 2 (Nrf2) and
mitogen‑activated protein kinase (MAPK) are controlled
by SFN. On the other hand, an overexpression of Nrf‑2
makes cancer cells resistant to few chemotherapeutic drugs
as observed by Xu et al.[32] The authors suggested that the
time and the dose of SFN regulating this pathway during
the cancer therapy need further research. This will eliminate
the possible side effects while utilizing the anticancer effects
of SFN. SFN enhances the effect of the chemotherapeutic
agents by smaller doses and limits the toxicity to healthy
normal cells.[32]
Researchers found that persons consuming broccoli
regularly though not daily, expressed higher levels of tumor
suppressor gene p16 than those who had no or few of
these vegetables in their diet. This was surprising because
SFN is cleared of the body within 24 h. This suggests that
the SFN and its metabolites trigger epigenetic mechanisms
in the body, which enhances protection from cancer even
when the substance is eliminated from the body.[33] SFN is
said to induce a protein called Nrf2 which in later stages
of development of cancer is believed to support the
tumor growth and cause plaque buildup in arteries. Thus,
a further investigation on the role of Nrf2 in cancer and
cardiovascular disease is needed.
SFN has shown to induce apoptosis in colon cancer,
prostate cancer, breast cancer, liver cancer and lung cancer
in mice. Although the benets of SFN are proved in
cell‑based, animal and some human trials, recommendations
are few. Hence, at present, SFN use is limited as an adjuvant
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to the conventional chemotherapy and radiotherapy.
It may be helpful in preventing recurrence among
head‑and‑neck cancer survivors. Sulphoraphane helps
in protecting against chronic exposure to environmental
pollutants and carcinogens. Bauman et al. performed
studies involving mice as well as humans and found some
adverse effects on the use of this substance.[34] SFN is
believed to cause autophagy in cancer cells. Treatment
of prostate cancer cell lines, PC‑3 and LNCap, with SFN
resulted in the upregulation, processing and recruitment
to autophagosomes of microtubule‑associated protein
light chain 3.[35]
The nuclear factor‑kappa B (NF‑κB) prevents tumor
growth by inhibiting proliferation, angiogenesis and
invasion. Inflammation is known to induce tumor
proliferation and reduce apoptosis, thereby increasing
the risk of tumor development. SFN is said to reduce the
secretion of inammatory cytokines from blood cells,
thereby preventing the action of NF‑κB on DNA.[36]
Unlike normal cells, cancer cells evade the DNA repair
mechanisms and rapidly divide propagating the defective
mutations, and they do not respond to the apoptotic cell
signals. Broccoli extracts trigger the apoptosis of cancer
cells activated by the mitochondria and also cause the
arrest of cell division in S and M phases, which was
not specic to any cell and tissue. This resulted in a
decrease in cell division cycle 25C and breakdown of
mitotic spindle assemblies. SFN is said to inhibit tubulin
polymerization.[37]
The activation of the MAPK/ERK pathway has been
reported after SFN treatment in a number of cell lines,
including PC3 cells, through the activation of the activator
protein‑1 (AP‑1) transcription factor which plays a role in
apoptosis.[38]
Tang et al. also showed that broccoli extracts had the
ability to prevent cancer cell proliferation, which was
attributed to the presence of these isothiocyanates.[9]
Further, SFN in broccoli induced the formation of Phase
2 enzymes. Broccoli extracts revealed antiproliferative
properties similar to SFN, suggesting that they can be
used as a replacement for SFN for potential clinical test
and use. Thus, the naturally available SFN rather than
the pharmaceutical agent would be easily available, and
involves less complex procedures of preparation, thereby
being much cheaper and cost‑effective. However, loss of
SFN while eating sprouts may result due to epithiospecier
protein. Further research to maintain the stability of these
extracts is needed.[9]
Angiogenesis is an important step in carcinogenesis,
which supports the rapidly dividing cancer cells. SFN is
said to inhibit the development of new blood vessels,
thereby depriving the tumor cells and limiting the tumor
growth. In addition, SFN prevents tumor invasion and
metastasis. SFN can prevent the development and growth
of hormone‑sensitive tumors such as breast and prostate
cancers.[6] Glucosinolate hydrolysis promotes the apoptosis
of cultured prostate cancer cell lines, thereby inhibiting the
growth of tumor. An inverse association between intake of
cruciferous vegetables and the risk of developing prostate
cancer was suggested.[39]
Cancer stem cells (CSCs) initiate and maintain the
cancer and are also responsible for recurrence and drug
resistance, which is prevented by SFN.[40] Li et al., 2017,
observed that SFN reduced the proliferation rate of
oral squamous cell carcinoma CSCs in a dose‑dependent
manner.[41] In addition, they noticed a limited effect on
the normal oral mucosal cell proliferation. CSCs of oral
cancer showed reduced migration, invasion, clonogenicity,
in vivo tumorigenicity and a dose‑dependent increase in
the level of tumor‑suppressive miR200c, suggesting that
SFN suppressed initiation and stemness in cancer CSCs.
This led to a decrease in tumor growth and prevented
new tumor development as observed both in in vitro
and in vivo animal experiments. SFN possibly targets
the CSCs in various cancers via alteration of NF‑κB,
epithelial–mesenchymal transition and Wnt/β‑catenin
pathways.[40] Researchers believed that SFN when used
as an adjuvant along with conventional chemotherapy
yielded better results.[41]
The assessment of SFN in the regulation of miRNA
expression is limited in the literature, and further
investigation is required in order to complete understanding.
The upregulation of miR‑23b and miR‑27b in colorectal
cancer cells was signicant by SFN.[42]
HPV‑induced cervical cancer and Helicobacter pylori‑induced
gastric cancer are established facts. SFN was effective in
preventing these cancers. SFN was found to be effective
in reducing the conversion of intraepithelial neoplasia into
cervical cancer in mice.[43] Further, SFN in puried form
was found to be effective in the eradication of the strain
in both mice and human trials.[44] The ability of SFN to
modulate toll‑like receptor (TLR) activation and signaling
has been implicated as an additional chemopreventive
property. Zhu et al. observed that SFN caused inhibition
of TLR3, with the ability to modulate NFjB signaling and
downstream gene expression, including the downregulation
of interleukin 8 and tumor necrosis factor‑alpha.[45]
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Studies on single urinary bladder cancer cell
lines (UM‑UC‑3 cells) have revealed that isothionyates
in broccoli extracts along with SFN possess certain
antiproliferative properties inhibiting the tumor growth.
The authors believed that this may possibly be observed
in other types of cancer as well. The risk of urothelial and
bladder cancers was signicantly more in individuals who
carried genetic variants of glutathione S‑transferase (GST)
or NQO1 that yielded either a null or a suboptimal
phenotype. This is not surprising, because both these
Phase 2 enzymes are important cellular protectants
against carcinogens and oxidants.[46] The ability of SFN
to sensitize drug‑resistant cancer cells to TNF‑related
apoptosis‑inducing ligand (TRAIL)‑induced apoptosis
has been demonstrated in multiple studies, with reports
demonstrating SFN‑enhanced TRAIL‑induced apoptosis
in human hepatoma cells.[47]
Thus, various studies have shown that SFN induces
mitochondria‑mediated cellular apoptosis, induces cell
cycle arrest, acts as antioxidant reducing the oxidative
stress, induces Nrf‑2 preventing inflammation and
cytokine secretion, inhibits histone deacetylase and DNA
methylation thereby altering epigenetic mechanism and
induces Phase 2 enzymes such as GST and quinone
oxidoreductase 1, thereby protecting the cells from DNA
damage caused by carcinogens and reactive oxygen species,
disrupting the oncogenic signaling pathways.
OTHER HEALTH BENEFITS OF SULFORAPHANE
SFN has other benecial effects in addition to cancer
protection. SFN exhibits neuroprotective effects and is
implemented in treating conditions such as traumatic
brain injury, Alzheimer’s disease and Parkinson’s disease.
Patients with autism have shown an improvement in social
interaction, abnormal behavior and verbal communication
after treatment with these compounds. SFN contains a
avonoid kaempferol which is effective in treating various
allergies.[6] Broccoli has Vitamin A and higher amounts
of ber, which improves the digestion and gut health.
It lowers cholesterol and combats ulcer‑causing H. pylori
bacteria in the digestive system. Broccoli extracts are said
to prevent and repair the skin damage caused by UV light,
however results on animal and human showed variation.
High levels of carotenoids, lutein and zeaxanthin support
eye health.[48] SFN supports detoxication because it has
amino acids, Vitamin C and sulfur. Further, SFN shows
anti‑inammatory effects, thus preventing many chronic
diseases such as colitis, arthritis, airway‑related problems
such as asthma and chronic obstructive pulmonary
disease. It provides important vitamins and minerals,
including magnesium, potassium, calcium, protein and
Vitamin C, which improves the bone health, delays aging,
boosts immunity and promotes hair growth. It prevents
nonalcoholic fatty liver. It also helps in preventing the
thickening of the arteries, thereby reducing the risk for
heart disease. SFN is also said to reduce cholesterol levels.[34]
Broccoli has a low glycemic index as it contains both soluble
ber and chromium, which is benecial in diabetic patients
when consumed in moderate quantity.[17,49,50]
ADVERSE EFFECTS
SFN acts as a double‑edge sword. Eating broccoli in
moderate quantity is benecial, however excess consumption
might lead to some side effects. Excess consumption in
diabetic patients may give rise to hypoglycemia. Possible
liver toxicity on intake of extreme doses has also been
reported. Side effects such as gastric irritation, irritable
bowel syndrome, diarrhea, abdominal pain and atulence
due to its high ber content have also been reported.
Isothiocyanates in broccoli are said to be goitrogens which
alter the uptake of iodine, thereby altering the function of
thyroid gland, resulting in hypothyroidism.[6] Broccoli has
numerous traces of pesticides, of which formaldehyde is
carcinogenic. It may cause allergic reactions such as skin
rashes, itching, nasal congestion, wheezing and headache
in some people. Smokers who consume excess broccoli
may be at risk for developing lung cancer due to excess
antioxidants. Risk of hemorrhagic stroke in persons with
excess broccoli consumption is linked to Vitamin E in
broccoli. Intake of too much potassium‑rich broccoli can
lead to the risk of hypotension. Vitamin K in broccoli
might alter blood clotting and increase bleeding risk in
patients having blood thinners if intake is excess. Thus,
consumption in extreme doses has shown some side
effects.[49] However, the health benets outweigh the side
effects when consumed in right amount.
CONCLUSION
Broccoli and its sprouts contain naturally occurring
isothiocyanates such as SFN with potent cancer‑ghting
properties. In vitro and animal experiments have extensively
studied the role of SFN in treating different types of cancers
as well as other diseases. Although commercial supplements
are available, they are not Food and Drug Administration
approved as yet. In addition, the pharmacokinetics and
side effects are widely being explored at present. Further
clinical studies and human trials related to their safety, side
effects, isolation and therapeutic dosage and frequency of
intake would provide an insight into the benecial effects
of these isothiocyanates. They provide an easily available,
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Nandini, et al.: Sulforaphane in broccoli
Journal of Oral and Maxillofacial Pathology | Volume 24 | Issue 2 | May-August 2020
cost‑effective alternative chemoprevention with little side
effects compared to the conventional chemotherapeutic
drugs. It is worthwhile to consume these vegetables in the
right amount on a regular basis to promote general health
and reduce the cancer risk.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conicts of interest.
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