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Exploring the anticancer potential of Boswellia serrata: A comprehensive review
Olabode Martins Olabintan 1, *, Yusuf Adekola Wahab 2 and Nurain Kehinde Ahmed 2
1 Department of Biochemistry, Cancer Research and Molecular Biology, University of Ibadan, Nigeria.
2 Department of Chemical Sciences, Faculty of Science, Olusegun Agagu University of Science and Technology, Nigeria.
GSC Biological and Pharmaceutical Sciences, 2024, 26(01), 349–362
Publication history: Received on 11 December 2023; revised on 26 January 2024; accepted on 29 January 2024
Article DOI: https://doi.org/10.30574/gscbps.2024.26.1.0027
Abstract
Plants are endowed with numerous phytochemicals and bioactive compounds which have been explored and reported
to possess therapeutic potential against different diseases. The aim of this review paper is to explore the anticancer
potential of Boswellia serrata. Cancer is known to be a burden on the global healthcare system while Boswellia serrata
has been reported to possess numerous bioactive compounds with anticancer effects. Therefore, there is a need to
further assess the applicability of Boswellia serrata as an anticancer. The included studies for review were accessed via
online databases such as Scopus, PubMed, and Google scholar with specified inclusion and exclusion criteria to guide
the study selection process. Following a critical content analysis, it was found that Boswellia serrata possesses numerous
bioactive compounds with anti-proliferative, cell cycle inhibitory, apoptosis, anti-metastatic, and anti-tumor effect. In
conclusion, Boswellia serrata holds a great potential in the treatment of cancer and can be a potent tool in the ongoing
fight against cancer; however, further studies are essential to understand the mechanism of actions of specific bioactive
compounds identified in Boswellia serrata.
Keywords: Anticancer; Boswellia serrata; Antimetastasis; Antitumor; Antiproliferative
1. Introduction
Globally, cancer has been a critical health issue and a burden to the healthcare system. In 2020, the World Health
Organization reported about 10 million deaths globally due to cancer with the most common types being colon, breast,
rectum, and prostate cancer [1]. This mortality rate has been forecasted to reach over 16 million by 2040 [2]. These
data strengthen the claim that cancer has become a global health concern that requires proactive response from
researchers, health professionals, governmental and non-governmental organizations, and other relevant stakeholders.
Cancer can also be referred to as malignant tumors or neoplasm, which can affect any part of the body [3]. It is
characterized by rapid and uncontrolled proliferation of abnormal cells, which have the capability to invade other body
parts and spread to other vital body organs through a process known as metastasis.
The transformation of normal cells into tumor cells involve a comprehensive stage and interaction between individual
genetic makeup and the external environment, which is constituted by carcinogenic agents [3, 4]. These carcinogenic
agents can be of either physical, chemical, or biological [5]. Choi and Hua [6] identified the risk factors of cancer and
reported that lifestyle has a crucial role to play in cancer cell formation. This lifestyle may include alcohol consumption,
tobacco use, physical inactivity, unhealthy diet, and many more. In addition, Roderburg et al. [7] reported that in 2018,
13% of the globally diagnosed cancer cases were attributed to chronic infections caused by Human Papilloma Virus
(HPV), hepatitis virus, Helicobacter pylori, and Epstein-Barr virus. Due to the complex nature of cancer, researchers have
continuously worked towards the discovery of therapeutic agents with anti-cancer properties [8]. These efforts include
the exploration of plants with medicinal properties. Similarly, the aim of this comprehensive review is to explore the
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anticancer potential of Boswellia serrata. The relevance of this is to contribute significantly to the ongoing effort to tackle
the incidence and prevalence of cancer.
Boswellia serrata has been reported as a plant with various medicinal properties [9]. It is native to regions such as Africa,
India, and the Arabian Peninsula, and widely used in Ayurveda, the traditional Indian medicinal system [9]. Boswellia
serrata belongs to the family Burseraceae and genus Boswellia. It grows on dry mountainous regions of India, Northern
Africa, and the Middle East [10]. The resinous part of the plant has been reported to contain monoterpenes (α-thujene),
diterpenes (incensole oxide), triterpenes (α- and β-amyrins), pentacyclic triterpenic acids, and tetracyclic triterpenic
acids [10]. Four pentacyclic triterpenic acids (Boswellic acids), extracted from the plants has been reported to possess
anti-inflammatory and anticancer potential [11]. It has also been reported to be a potential anticancer agent [10]. In
addition, the gum resin of Boswellia serrata has been shown to increase symptoms in patients with rheumatoid arthritis
and osteoarthritis [12]. These are indications that Boswellia serrata possesses various medicinal properties and
therefore, could be a potential therapeutic agent against cancer. This comprehensive review delves into the anticancer
potential of Boswellia serrata by investigating its antiproliferative, cell cycle inhibitory, apoptosis, anti-metastatic, and
anti-tumor potential. The finding of this report is relevant to the ongoing effort to drastically reduce cancer incidence,
prevalence, and mortality rate.
2. Method
The methodology adopted by this study is a comprehensive review of scientific literature, which were accessed via
online databases such as Scopus, PubMed, Google scholar, and Biomed central. Access to relevant resources via these
databases provided insight into the medicinal use of Boswellia serrata within the context of cancer. Furthermore,
relevant websites such as www.theplantlist.org and www.ipni.org provided vital information about the dynamics and
potential of Boswellia serrata. The various resources included for critical review are published articles, thesis, abstract,
published books, and conference proceedings.
The inclusion criteria, which served as a guide for the study selection process, include studies published between 2010
to 2024, studies published in English language, and studies that focus on either cancer, Boswellia serrata, or both. On
the other hand, studies published earlier than 2010, in language other than English, and without a focus on the
anticancer potential of Boswellia serrata were excluded. A critical aspect of the study selection process was the
prioritization of only quality studies that have satisfied the inclusion criteria. Search terms include “Boswellia serrata,”
“anticancer properties,” “Boswellia serrata and cancer,” “anti-proliferation,” “cell cycle inhibition,” “apoptosis inducer,”
“anti-metastatic potential,” and “anti-tumor effect”. The major findings extracted from the included studies are then
systematically presented in this report.
3. Discussions
This section discusses the major findings from a critical review and analysis of the included studies. These findings are
presented in the subsections below:
3.1. Overview of Boswellia serrata
Boswellia serrata, commonly known as Indian Frankincense is an indigenous traditional plant to India, Asia and
Northern Africa. It is known for its medicinal, commercial and religious uses, hence making it a highly valued plant. It
belongs to the family of Burseraceae and has been used for centuries in traditional Ayurvedic medicine in the treatment
of a variety of diseases such as Osteoarthritis, Inflammatory bowel disease, Asthma, and Rheumatoid arthritis [13].
Trade routes stretching from Dhofar (Oman), Qarn (Yemen), to Saukin (Ethiopia) facilitated the exchange of Boswellia
resin with empires like Persian, Greek, Babylonian, Chinese, and Mesopotamian. Boswellia serrata resin, among others,
held substantial value in these ancient trade networks, contributing to cultural and economic interactions among varied
civilizations [14,15].
Boswellia trees, known for their deciduous nature, can grow to heights exceeding 5 meters, influenced significantly by
their species and the surrounding conditions. These trees present smooth stems and branches, with bark that sheds,
giving them the appearance of either a bush or a tree [16]. It often reaches a height of 9 to 15 metres and a diameter of
1.2 to 1.8 metres. The thin bark has ashy, reddish, or greyish-green tones, and under its outer layer lies a layer of
chlorophyll that peels off in tiny, papery flakes. Their fruits are typically 1.3 centimeters long, trigonous, and has three
valves, three heart-shaped, one-seeded pyrenes, and wings along the edges. B. serrata has alternating, stipule-free,
imparipinnate leaves that range in length from 20 to 45 centimeters. These leaves tend to cluster towards the tips of
branches, with leaflets spanning 17-31 cm. The leaflets are positioned opposite each other, varying in size from 2.5-8
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cm in width and 0.8-1.5 cm in breadth, with the lower pairs often being the smallest. They exhibit significant variety in
their size and are sessile, lanceolate, ovate-lanceolate, and have an uneven, notched border [17]. Both the exudate from
its bark (resin of the oleo gum) and leaf extracts have shown various biological activities such as anti-inflammatory,
anti-oxidant and anti-cancer [18,19,20]. Table 1 presents the taxonomical hierarchy while Table 2 presents the
geographical nomenclature of Boswellia serrata
Table 1 Taxonomical Hierarchy of Boswellia serrata
Kingdom
Plantae
Phylum
Tracheobionta
Class
Magnoliophyta
Order
Magnoliopsida
Family
Sapindales
Genus
Burseraceae
Species
Boswellia serrata
(Source: [21])
Table 2 The geographical nomenclatures of Boswellia serrata tree
English
Indian Olibanum, Indian Frankincense
India/Hindi
Salai
Bengali
Kundur, salai
Arabic
Kondor, luban dhakar
Telugu
Andugum chettu
(Source: [21])
Figure 1 Boswellia serrata tree in its Natural Habitat (Source: Forrest Ecology)
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3.2. Bioactive Compounds of Boswellia serrata
The Oleo gum resin of Boswellia serrata has been analyzed by various studies in an attempt to understand the various
bioactive compounds that constitute the medicinal plant. According to Sudhanshu et al. [22] the plant possesses several
pharmacologically active elements such as terpenoids and oil. However, several factors affect the chemical composition
of the plant and these include species, age, resin quality, and geographic location [23]. Specifically, the oleo gum contains
resins (30–60%), essential oil (5–10%), and water-soluble polysaccharides (~65% arabinose, galactose, and xylose)
[22]. Hanaa et al. [24] conducted a GC/MS analysis of unsaponifiable matter of petroleum ether extract of B. serrata
oleum gum resin and the bioactive compounds discovered are presented in Table 3. The study also analyzed fatty acid
methyl esters of petroleum ether extract of the plant with the identified bioactive compounds presented in Table 4.
Lastly, the compounds identified through a GC/MS analysis of the volatile oils of B. serrata Oleo gum resin and 11
bioactive compounds were identified (Table 5).
Boswellia serrata is known for containing resinous compounds, and the identified hydrocarbons are likely components
of the resin. These hydrocarbons contribute to the overall chemical profile of the gum resin. Sterols are common
components in plant resins and oleo-gum resins. Cholesterol, stigmasterol, and β-sitosterol are plant sterols that may
have physiological roles in the plant and can be transferred to the oleo-gum resin [10]. The significant presence of
tricosane (75.32%) suggests that it is a major constituent of the unsaponifiable matter in Boswellia serrata [24].
Tricosane may contribute to the resin's properties and play a role in its biological functions. The justification for the
presence of these compounds lies in the plant's biosynthetic pathways and ecological functions. Hydrocarbons are often
synthesized as part of resinous compounds that protect plants from herbivores and pathogens [25]. Sterols, on the other
hand, are essential components of cell membranes and play various roles in plant physiology [26]. This is presented in
Table 3 below
Table 3 GC/MS analysis of unsaponifiable matter of petroleum ether extract of B. serrata oleum gum resin
Retention Time
Compound
Composition (%)
Structure
17.22
Eicosane
3.19
17.92
Heneicosane
4.61
20.91
Tricosane
75.32
21.75
Tetracosane
8.47
22.51
Pentacosane
2.67
23.34
Hexacosane
2.58
24.61
Octacosane
1.16
27.91
Triacontane
1.11
28.72
Cholesterol
0.14
30.07
Stigmasterol
0.58
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30.73
β-Sitosterol
0.17
(Sources: 24; 10)
The GC/MS analysis of the fatty acids methyl esters (FAMEs) in the petroleum ether extract of Boswellia serrata oleo-
gum resin reveals a diverse and intricate chemical composition. The identified compounds include both saturated and
unsaturated fatty acids, with Lauric acid (C12:0), Myristoleic acid (C14:1), Palmitoleic acid (C16:1), Oleic acid (C18:1),
and Linoleic acid (C18:2) being among the major constituents [24]. These fatty acids are known for their various
biological activities, including antimicrobial, anti-inflammatory, and cardiovascular benefits [27]. The presence of
Lauric acid suggests a potential role in the plant's defense against microbial threats, while Myristoleic acid and
Palmitoleic acid may contribute to anti-inflammatory and skin health properties [28]. Oleic acid, a common
monounsaturated fatty acid, is abundant and likely contributes to the overall health-promoting characteristics of the
resin. Additionally, the presence of essential fatty acids like Linoleic acid and Linolenic acid underscores the nutritional
value of Boswellia serrata oleo-gum resin. The resin also contains long-chain polyunsaturated fatty acids, such as
Arachidonic acid and Eicosapentaenoic acid, which are precursors to bioactive lipid mediators involved in inflammation
and immune response [29]. This is presented in Table 4 below
Table 4 GC/MS Analysis of Fatty Acids Methyl Esters of Petroleum ether Extract of B. serrata Oleo Gum Resin
Retention
Time
Compound
Composition
(%)
Structure
6.05
Caproic acid (C6:0)
0.08
15.06
Capric acid (C10:0)
0.51
18.27
Lauric acid (C12:0)
9.38
19.63
Tridecanoic acid (C13:0)
0.68
21.32
Myristic acid (C14:0)
0.32
22.03
Myristoleic acid (C14:1)
9.3
24.3
Pentadecanoic acid (C15:0)
0.51
28.17
Palmitic acid (C16:0)
2.24
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29.38
Palmitoleic acid (C16:1)
22.41
31.62
Margaric acid (C17:0)
4.54
33.1
Stearic acid (C18:0)
3.02
34.79
Oleic acid (C18:1)
30.05
35.41
Linoleic acid (C18:2)
3.39
35.92
Linolenic acid (C18:3)
1.61
40.8
Arachidic acid (C20:0)
1.6
41.23
11,14,17-Eicosatrienoic acid (C20:3)
2.38
42.05
Arachidonic acid (C20:4)
3.2
44.56
5,8,11,14,17-Eicosapentaenoic acid
(C20:5)
1.91
45.17
Heneicosanoic acid (C21:0)
1.8
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48.55
Tricosanoic acid (C23:0)
0.68
50.36
Tetracosanoic acid (C24:0)
0.27
(Sources: 24; 10)
The GC/MS analysis of the volatile oils in Boswellia serrata oleo-gum resin reveals a diverse array of compounds, each
contributing to the resin's unique aromatic profile. Sabinene dominates the composition at 19.11%, suggesting a
prominent role in defining the resin's fragrance [24]. Terpinen-4-ol and β-Copaen-4-α-ol follow closely, with
percentages ranging from 10.24% to 14.64%, contributing to the overall complexity of the volatile oil blend [10].
Terpinyl acetate, a terpene ester at 13.01%, enhances the aromatic richness of the resin. Additional compounds such as
Elemicin, Germacrene D, and β-Caryophyllene contribute to the resin's volatile oil composition, each adding distinct
olfactory and potentially therapeutic characteristics [23]. The presence of these volatile oils suggests potential
applications in traditional medicine and perfumery, aligning with the resin's historical uses. The resin's aromatic
complexity, derived from compounds like Chavicol, Linalool, and α– Thujene, further underscores its potential
versatility in various applications. This is presented in Table 5 below
Table 5 GC/MS Analysis of the Volatile Oils of B. serrata Oleo gum Resin
Retention Time
Compound
Composition (%)
Structure
6.74
α– Thujene
1.29
9.13
Sabinene
19.11
13.52
Terpinen-4-ol
14.64
16.2
cis-Carveol
6.26
16.9
Chavicol
4.75
18
Linalool
1.02
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22.37
Terpinyl acetate
13.01
24.1
β-Caryophyllene
3.03
31.2
Elemicin
7.05
31.43
β-Copaen-4-α-ol
10.24
37.13
Germacrene D
12.6
(Sources: 24; 10)
3.3. Anticancer Potential
The focus on plant-based treatments in cancer research is promising due to the presence of chemical constituents within
plants showing a more targeted effect on cancer cells while potentially minimizing harm to healthy cells. This targeted
action is one of the key aspects that make plant-based therapies an exciting area of exploration in cancer treatment.
Boswellia serrata demonstrates a multifaceted anti-cancer mechanism, encompassing cell cycle inhibition, apoptosis
induction, anti-proliferative effects, and exerting anti-tumor actions. [29, 30].
3.3.1. Anti-Proliferative Effects
The antiproliferative effects of Boswellia serrata, particularly its boswellic acids, have been explored in clinical trials
and in-vitro studies. The process by which a cell grows and divides to produce two daughter cells is known as cell
proliferation. It encompasses the fusion of the cell cycle and growth, resulting in a large number of diploid cell progenies.
The external growth factors and the intracellular gene regulatory network closely regulate this process. Cancer cells are
recognized for their capability to evade growth suppressors, leading to traits such as replicative immortality and
continuous cell proliferation [31, 32].
Current research findings in clinical trials for patients with breast cancer suggest that the boswellic acids derived from
Boswellia serrata exhibit potential antiproliferative effects. According to Valente et al. [31], an early-phase clinical trial
was conducted to investigate the biological activity and safety of Boswellia serrata (B. serrata) in patients with invasive
breast cancer, prior surgery, patients were administered an oral dose of 2400 mg/day. The examination of diagnostic
and post-treatment tissues revealed a significant decrease (13.8%) in proliferation (Ki-67 index), contrasting with the
control group which showed an increase in proliferation (54.6%). The administration of B. serrata was reported to be
well-tolerated, with no adverse events recorded [31].
In an in-vitro study by Shao et al. [32] on the Inhibitory Activity of Boswellic Acids from Boswellia serrata against Human
Leukemia HL-60 Cells in Culture, four Boswellic acids compounds (β-3-Boswellic acid, 3-O-Acetyl-β-3-boswellic acid,
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11-Keto-β-3-boswellic acid, and 3-O-Acetyl-1l-keto-β-3-boswellic acid) were isolated from Boswellia serrata oleogum
resin. Their inhibitory activity was demonstrated in Human Leukemia HL-60 Cells and a dose-dependent inhibition of
DNA, RNA, and protein synthesis in HL-60 cells was reported [32]. These findings suggest the potential of Boswellia
serrata in exerting antiproliferative effects, making it a subject of interest for further research and development in
cancer therapy.
3.3.2. Cell Cycle Inhibitory Activities
Cell cycle inhibition, which can happen at different phases of the cell cycle, is crucial for preserving healthy cell function
and halting the uncontrolled proliferation of cells. DNA synthesis and chromosome segregation are carefully monitored
at cell cycle checkpoints to detect abnormalities (mutation). If mutation is detected in a normal cell undergoing the cell
cycle, the cell cycle will arrest to allow for the repair of the mutation before re-entering the cell cycle. In contrast, cancer
cells can harbor mutations in their DNA yet undergo cell cycle without arrest [33, 34].
The findings of a previous study conducted by Lv et al. [35] have indicated that Acetyl-11-keto-β-boswellic acid (AKBA)
can enhance the sensitivity of cisplatin (CDDP) by inducing G0/G1 phase arrest in A549 cells. To assess the impact of
AKBA, CDDP alone, and their combination on the cell cycle in A549 cells, flow cytometry was employed. After a 48-hour
cotreatment with AKBA and CDDP, flow cytometry analysis revealed an increase in the percentages of cells in the G0/G1
phase and a reduction in the frequencies of cells in the G2/M phase compared to CDDP alone. This suggests that the
combined treatment inhibits the transition of cells from the G0/G1 phase to the G2/M phase in the cell cycle [35].
It was also reported in another investigation by Lv et al. [35] that AKBA Induced the Cell Cycle Arrest at G0/G1 Phase in
Human NSCLC Cell Line A549. Flow cytometry analysis was conducted to assess the cell cycle distribution in A549 cells
treated with different concentrations of AKBA (0, 5, 10 μg/mL). Their result indicated that AKBA led to an increase in
the percentage of cells in the G0/G1 phase and a decrease in the S phase at the concentration of 10 μg/mL. The
percentage of cells in the G2/M phase, however, barely changed. The Western blotting technique was also utilized to
examine the levels of cell cycle proteins/cell cycle regulators, and it was reported that AKBA downregulated the
expression levels of cyclin A2 and cyclin E1. The investigation of the expression of the cell cycle protein further aligned
with the results obtained from flow cytometry, providing additional evidence of AKBA's inhibitory effect [36]. These
findings strongly suggest that AKBA can inhibit tumor cell growth by inducing cell cycle arrest specifically at the G0/G1
phase.
3.3.3. Apoptosis Inducer
Apoptosis, a tightly regulated mechanism of programmed cell death, is crucial for maintaining tissue homeostasis and
eliminating damaged or unnecessary cells [37], such as those resulting from DNA damage or during development [38,
39]. Many Phyto-compounds have been investigated for their potential to induce apoptosis, among them is Acetyl-11-
keto-β-boswellic acid (AKBA), a pentacyclic terpenoid derived from the resin of the Ayurvedic medicinal plant Boswellia
serrata [40]. AKBA, known for its anti-inflammatory properties, demonstrates significant cytotoxic effects on various
human cancer cell lines, including glioblastoma, meningioma, leukemia, breast, liver, fibrosarcoma, melanoma, colon,
prostate, and pancreatic cancer cells [41- 45], through the activation of caspase-3 and caspase-8 as well as with poly
(ADP) ribose polymerase (PARP) cleavage [46, 47] and the modulation of the death receptor 5-mediated signaling
pathway [47].
Previous studies have shown a significant increase in apoptosis within colorectal [43 - 48] breast [49] oral squamous
cell [50] carcinomas, upon administration of oleoresin from Boswellia species extract, particularly Boswellia serrata.
However, the precise pathways and molecular mechanisms underlying the process remain unclear [51]. In 2002, Liu et
al. conducted a study (as cited in [47]) examining the apoptotic and antiproliferative impacts of three principal
components of Boswellia serrata extract - β-boswellic acid (BA), keto-β-boswellic acid (K-BA), and acetyl-keto-β-
boswellic acid (AK-BA) - on colon cancer HT-29 cells, which are a line of human colorectal adenocarcinoma cells.
The results revealed that both K-BA and AK-BA dose- dependently increased the cytoplasmic DNA–histone complex in
HT-29 cells, with AK-BA exhibiting a stronger effect than K-BA. BA only showed an apoptotic effect at the highest
concentration tested. Flow cytometry analysis showed that after incubation with 100 μM K-BA and AK-BA for 24 hours,
the number of apoptotic cells significantly increased, with AK-BA inducing a larger proportion of sub-G1 cells compared
to K-BA. However, BA did not show a significant increase in the sub-G1 peak at the same concentration. To further
confirm the apoptotic effects of BA in HT-29 cells, Liu and his colleagues evaluated the activation of caspase-3 induced
by AK-BA compared to camptothecin. The results indicated that at 50 μM, both effects of AK-BA were more than 3-fold
greater than those induced by camptothecin. In the same year, Liu and his team also investigated the impact of BA, K-
BA, and AK-BA on Hep G2 cells (as cited by [47], [52]). The findings indicated that a 100 μM concentration of AK-BA
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significantly elevated the sub-G1 peak, whereas K-BA did not exhibit a notable apoptotic effect at the same
concentration.
Conti et al. [41] also observed that the treatment of 30 μM AKBA to A172 cells resulted in a 12% increase in apoptotic
cells compared to the 3% observed in untreated cells. Similarly, Li et al. [53] conducted a study examining the
mechanism of AKBA-induced apoptosis, measuring caspase-3/7 activity and analyzing the cleavage of caspase 3 and
PARP. Their findings demonstrated an elevation in the percentages of early apoptotic, late apoptotic, and necrotic cells
in U251 and U87-MG cells following AKBA treatment.
3.3.4. Anti-Tumor Effects
Boswellic acid and its structurally related derivatives have been documented to be effective as an anti-inflammatory,
hypolipidemic, and immunomodulatory [54]. Various triterpenoid acids identified in both B. serrata and B. carterii have
been recognized for their anti-proliferative properties [55], and in vivo studies have also confirmed that AKBA possesses
anti-carcinogenic and anti-tumor properties [20, 21, 53]. A study conducted by Li et al. [53] showed a significant
inhibition by AKBA in the migration and invasion of U251 and U87-MG cells and also reduced colony formation observed
in cells treated with 10, 20, and 30 μM AKBA compared to the control group, suggesting that AKBA has the potential to
significantly block the metastatic biological functions of glioblastoma cells. Acetyl-11-keto-beta-boswellic acid (AKBA)
exhibited greater efficacy in inhibiting cancer cell growth compared to the isolated pure form of 3-O- acetyl-11-keto-
beta-boswellic acid, as reported by Al-Yasiry and Kiczorowska [55].
Conti et al. [41] investigated the combined impact of AKBA and ionizing radiation on the viability of glioblastoma cells,
including U87, U251, LN319, and A172. The study involved irradiating the cells with varying doses (2, 4, or 6 Gy)
followed by exposure to different AKBA concentrations (10–50 μM) for 72 hours. AKBA treatment demonstrated a dose-
dependent inhibition of survival across all tested cell lines (10–50 μM). A172 and LN319 cells exhibited higher
susceptibility to the treatment compared to U87 and U251 cells. Notably, AKBA significantly reduced the survival of
A172 cells by over 50% at a concentration of 30 μM, while the inhibitory effect in the other three cell lines was achieved
at the higher AKBA concentration of 40 μM. The study suggested that the combination of radiation and Boswellia serrata
extract (AKBA) could be a potential cancer treatment, exhibiting a more substantial inhibitory effect compared to
radiation alone. Existing evidence supports the anti-cancer potential of boswellic acid against various malignant tumors,
with numerous semi-synthetic boswellic acids showing notable cytotoxic effects [11, 56-58].
3.3.5. Anti-Metastasis Potential
Metastasis, a hallmark of cancer progression, involves the spread of cancer cells from the primary tumor to distant sites,
contributing significantly to the malignancy of the disease [59]. Targeting metastasis is recognized as promising for
advancing cancer treatment, as emphasized by Esposito et al. [60], and numerous medicinal plants have been
investigated for their potential capabilities in inhibiting metastasis in various tumor cancers (breast, hepatic, colon, and
stomach cancer) [61, 62]. A study conducted by Yadav et al. [63] revealed that the oral intake of AKBA at doses ranging
from 50 to 200 mg/kg exhibited a dose-dependent suppression of colorectal cancer (CRC) tumor growth in mice. This
led to a reduction in tumor volumes (8.91 ± 0.41 mm3 to 4.16 ± 0.19 mm3) compared to mice treated with the vehicle. It
was also observed that AKBA exhibited high efficacy in suppressing ascites and distant metastasis to the liver, lungs,
and spleen in orthotopically implanted tumors in nude mice when compared to the control group.
Several studies have suggested that cancer cells possess chemokine receptors responsible for facilitating metastasis to
specific organs where their corresponding chemokines are expressed [64]. Chemokines and their receptors have been
identified to play a key role in the initiation or progression of cancers of the lung, colon, liver, breast, cervix, prostate,
bladder, ovary, esophagus, skin, and lymphatics cancer [65]. Early work has shown elevated expression levels of
chemokine receptors, namely CXCR4, CCR7, CCR9, and CCR10, in cancer cells originating from various solid tumor types
[66]. Among the most studied chemokines involved in tumor cell migration and metastasis is stromal cell-derived factor
1α (SDF-1 α, also recognized as CXC chemokine ligand 12 [CXCL12]) and its corresponding receptor, CXCR4. In a study
led by Park [67], the investigation focused on whether AKBA could influence the expression of CXCR4, thereby
hindering tumor cell invasion. The findings show that AKBA effectively downregulates constitutive CXCR4 expression
in various tumor cells characterized by an overexpression of this chemokine receptor, which led to the inhibition of
CXCL12-induced invasion in pancreatic (AsPC-1, BxPC-3, MIA PaCa-2, and PANC-28) and breast (MDA-MB-231,
MCF7/Neo, MCF7/HER2, SKBR3) cancer cells. Also, when treated with 50 μmol/L AKBA for 12 hours, AKBA
demonstrated the ability to downregulate CXCR4 expression in leukemia (KBM-5), kidney (A293), and multiple
myeloma (U266) cancer cell lines. However, it is noteworthy that the extent of CXCR4 downregulation by AKBA is not
uniform but depends on the specific cell type.
GSC Biological and Pharmaceutical Sciences, 2024, 26(01), 349–362
359
4. Conclusion
This report has provided a comprehensive insight into the therapeutic potential of Boswellia serrata as an anticancer
agent. Through a systematic review of relevant studies, this report has further strengthened the claim that Boswellia
serrata possesses numerous bioactive compounds with anti-proliferative, cell cycle inhibitory, apoptosis, anti-
metastatic, and anti-tumor effect. However, further studies are essential to understand the mechanism of actions of
specific bioactive compounds identified in Boswellia serrata.
Compliance with ethical standards
Disclosure of conflict of interest
No conflict of interest to be disclosed.
References
[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020:
GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer Journal
for Clinicians. 2021; 71(3):209-249.
[2] Dunn J. It Is Time to Close the Gap in Cancer Care. JCO Global Oncology. 2023; 9:e2200429.
[3] Brown JS, Amend SR, Austin RH, Gatenby RA, Hammarlund EU, Pienta KJ. Updating the Definition of Cancer.
Molecular Cancer Research. 2023; 21(11):1142-1147.
[4] Costello LC, Franklin RB. The genetic/metabolic transformation concept of carcinogenesis. Cancer Metastasis
Review. 2012; 31(1-2):123-30.
[5] Barnes JL, Zubair M, John K, Poirier MC, Martin FL. Carcinogens and DNA damage. Biochemical Society
Transaction. 2018; 46(5):1213-1224.
[6] Choi JW, Hua TNM. Impact of Lifestyle Behaviors on Cancer Risk and Prevention. Journal of Lifestyle Medicine.
2021; 11(1):1-7.
[7] Roderburg C, Krieg S, Krieg A, Luedde T, Kostev K, Loosen SH. The Association between Infectious Mononucleosis
and Cancer: A Cohort Study of 24,190 Outpatients in Germany. Cancers (Basel). 2022; 14(23):5837.
[8] Rehman FU, Al-Waeel M, Naz SS, Shah KU. Anticancer therapeutics: a brief account on wide refinements.
American Journal of Cancer Research. 2020; 10(11):3599-3621.
[9] Roy NK, Parama D, Banik K, Bordoloi D, Devi AK, Thakur KK, Padmavathi G, Shakibaei M, Fan L, Sethi G,
Kunnumakkara AB. An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases.
International Journal of Molecular Science. 2019; 20(17):4101.
[10] Siddiqui MZ. Boswellia serrata, a potential anti-inflammatory agent: an overview. Indian Journal of
Pharmaceutical Science. 2011; 73(3):255-61.
[11] Trivedi VL, Soni R, Dhyani P, Sati P, Tejada S, Sureda A, Setzer WN, Faizal Abdull Razis A, Modu B, Butnariu M,
Sharifi-Rad J. Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent. Frontiers
in Pharmacology. 2023; 14:1187181.
[12] Wang Z, Singh A, Jones G, Aitken D, Laslett LL, Hussain S, García-Molina P, Ding C, Antony B. Boswellia for
osteoarthritis. Cochrane Database of Systematic Review. 2022; 2022(10):CD014969.
[13] LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National
Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Boswellia serrata. 2020 Nov 4. PMID: 33151656.
[14] Al-Harrasi, A., Khan, A.L., Asaf, S., Al-Rawahi, A. (2019). Frankincense and Human Civilization: A Historical
Review. In: Biology of Genus Boswellia. Springer, Cham. https://doi.org/10.1007/978-3-030-16725-7_1
[15] Brendler T, Brinckmann JA, Schippmann U. Sustainable supply, a foundation for natural product development:
The case of Indian frankincense (Boswellia serrata Roxb. ex Colebr.). J Ethnopharmacol. 2018 Oct 28;225:279-
286.
GSC Biological and Pharmaceutical Sciences, 2024, 26(01), 349–362
360
[16] Paul, Michael. (2012). Chemotaxonomic Investigations on Resins of the Frankincense Species Boswellia
papyrifera, Boswellia serrata and Boswellia sacra, respectively, Boswellia carterii - A Qualitative and Quantitative
Approach by Chromatographic and Spectroscopic Methodology. 10.13140/RG.2.1.2108.7847.
[17] Orwa C, A Mutua, Kindt R , Jamnadass R, S Anthony. 2009 Agroforestree Database:a tree reference and selection
guide version (http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp)
[18] Gupta, M.; Rout, P.; Misra, L.; Gupta, P.; Singh, N.; Darokar, M.; Saikia, D.; Singh, S.; Bhakuni, R. Chemical
Composition and Bioactivity of Boswellia serrata Essential Oil in Relation to Geographical Variation Roxb. Plant
Biosystems 2016, 151(4), 623–629.
[19] Menon, M.; Kar, A. Analgesic and Psychopharmacological Effects of the Gum Resin of Boswellia serrata. Planta
Medicine 1971, 19(02), 333–341
[20] Mothana, R. A.; Hasson, S. S.; Schultze, W.; Mowitz, A.; Lindequist, U. Phytochemical Composition and in Vitro
Antimicrobial and Antioxidant Activities of Essential Oils of Three Endemic Soqotraen Boswellia Species. Food
Chemistry 2011, 126(3), 1149–1154,
[21] Al-Harrasi A, Khan AL, Asaf S, Al-Rawahi A. Biology of Genus Boswellia. Berlin, Germany: Springer; 2019
[22] Sudhanshu M, Ram SB, Rahul M, Deepti J. Boswellia serrata Roxb. – A Bioactive Herb with Various
Pharmacological Activities. Asian J Pharm Clin Res. 2020; 13(11):33-39
[23] Al-Harrasi A, Rehman NU, Khan AL, Al-Broumi M, Al-Amri I, Hussain J, Hussain H, Csuk R. Chemical, molecular
and structural studies of Boswellia species: β-Boswellic Aldehyde and 3-epi-11β-Dihydroxy BA as precursors in
biosynthesis of boswellic acids. PLoS One. 2018; 13(6):e0198666.
[24] Hanaa HA, Ahmed AA, Amal ZH, Soheir EK. Phytochemical Analysis and Anti-cancer Investigation of Boswellia
serrata Bioactive Constituents In Vitro. Asian Pacific Journal of Cancer Prevention. 2015; 16(8)
[25] Dutta S, Mehrotra RC, Paul S, Tiwari RP, Bhattacharya S, Srivastava G, Ralte VZ, Zoramthara C. Remarkable
preservation of terpenoids and record of volatile signalling in plant-animal interactions from Miocene amber. Sci
Rep. 2017; 7(1):10940.
[26] Du Y, Fu X, Chu Y, Wu P, Liu Y, Ma L, Tian H, Zhu B. Biosynthesis and the Roles of Plant Sterols in Development
and Stress Responses. Int J Mol Sci. 2022; 23(4):2332.
[27] Balta I, Stef L, Pet I, Iancu T, Stef D, Corcionivoschi N. Essential Fatty Acids as Biomedicines in Cardiac Health.
Biomedicines. 2021; 9(10):1466.
[28] Lin TK, Zhong L, Santiago JL. Anti-Inflammatory and Skin Barrier Repair Effects of Topical Application of Some
Plant Oils. Int J Mol Sci. 2017; 19(1), 70.
[29] J.J. Liu, R.D. Duan, LY294002 enhances boswellic acid-induced apoptosis in colon cancer cells, Anticancer Res. 29
(2009) 2987–2991
[30] Pang X, Yi Z, Zhang X, Sung B, Qu W, Lian X, Aggarwal BB, Liu M. Acetyl-11-keto-beta-boswellic acid inhibits
prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.
Cancer Res. 2009 Jul 15;69(14):5893-900.
[31] Valente IVB, Garcia D, Abbott A, Spruill L, Siegel J, Forcucci J, Hanna G, Mukherjee R, Hamann M, Hilliard E, Lockett
M, Cole DJ, Klauber-DeMore N. The anti-proliferative effects of a frankincense extract in a window of opportunity
phase ia clinical trial for patients with breast cancer. Breast Cancer Res Treat. 2024 Jan 9.
[32] Shao Y, Ho CT, Chin CK, Badmaev V, Ma W, Huang MT. Inhibitory activity of boswellic acids from Boswellia serrata
against human leukemia HL-60 cells in culture. Planta Med. 1998 May;64(4):328-31
[33] Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-
66.
[34] Torgovnick A, Schumacher B. DNA repair mechanisms in cancer development and therapy. Front Genet. 2015
Apr 23;6:157.
[35] Lv M, Zhuang X, Zhang Q, Cheng Y, Wu D, Wang X, Qiao T. Acetyl-11-keto-β-boswellic acid enhances the cisplatin
sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy
suppression via p21-dependent signaling pathway. Cell Biol Toxicol. 2021 Apr;37(2):209-228.
GSC Biological and Pharmaceutical Sciences, 2024, 26(01), 349–362
361
[36] Lv M, Shao S, Zhang Q, Zhuang X, Qiao T. Acetyl-11-Keto-β-Boswellic Acid Exerts the Anti-Cancer Effects via Cell
Cycle Arrest, Apoptosis Induction and Autophagy Suppression in Non-Small Cell Lung Cancer Cells. Onco Targets
Ther. 2020 Jan 23;13:733-744.
[37] Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D'Orazi G. Apoptosis as anticancer mechanism: function and
dysfunction of its modulators and targeted therapeutic strategies. Aging. 2016;8(4):603-619.
[38] Majtnerová P, Roušar T. An overview of apoptosis assays detecting DNA fragmentation. Mol Biol Rep.
2018;45(5):1469-1478.
[39] Green DR, L la mb i F. Cell D ea th Signaling. Cold Spring Harb Perspect Biol. 2015;7(12):a006080.
[40] Kumar A, Sharma S, Mishra S, Ojha S, Upadhyay P. ADME Prediction, Structure-activity Relationship of Boswellic
Acid Scaffold for the Aspect of Anticancer & Anti- inflammatory Potency. Anticancer Agents Med Chem.
2023;23(13):1499-1505.
[41] Conti S, Vexler A, Edry-Botzer L, Kalich-Philosoph L, Corn BW, Shtraus N, Meir Y, Hagoel L, Shtabsky A, Marmor
S, Earon G, Lev-Ari S. Combined acetyl-11-keto-β- boswellic acid and radiation treatment inhibited glioblastoma
tumor cells. PLoS One. 2018;13(7):e0198627.
[42] Suhail MM, Wu W, Cao A, Mondalek FG, Fung K-M, Shih P-T, et al. Boswellia sacra essential oil induces tumor cell-
specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells. BMC Complement
Altern Med. 2011;11:129.
[43] Ranjbarnejad T, Saidijam M, Moradkhani S, Najafi R. Methanolic extract of Boswellia serrata exhibits anti-cancer
activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells. Prostaglandins
Other Lipid Mediat. 2017;131:1-8.
[44] Liu YQ, Wang SK, Xu QQ, Yuan HQ, Guo YX, Wang Q, Kong F, Lin ZM, Sun DQ, Wang RM, Lou HX. Acetyl-11-keto-β-
boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3
signaling, thus suppressing chemoresistant stem cell-like properties. Acta Pharmacol Sin. 2019;40(5):689-698.
[45] Park B, Prasad S, Yadav V, Sung B, Aggarwal BB. Boswellic acid suppresses growth and metastasis of human
pancreatic tumors in an orthotopic nude mouse model through modulation of multiple targets. PLoS One.
2011;6(10):e26943.
[46] Ahmed SA, Al-Shanon AF, Al-Saffar AZ, Tawang A, Al-Obaidi JR. Antiproliferative and cell cycle arrest potentials of
3-O-acetyl-11-keto-β-boswellic acid against MCF-7 cells in vitro. J Genet Eng Biotechnol. 2023;21(1):75.
[47] Ragab EA, Abd El-Wahab MF, Doghish AS, et al. The journey of boswellic acids from synthesis to pharmacological
activities. Naunyn-Schmiedeberg's Arch Pharmacol. 2023.
[48] Ahmed HH, Abd-Rabou AA, Hassan AZ, Kotob SE. Phytochemical analysis and anti- cancer investigation of
Boswellia serrata bioactive constituents in vitro. Asian Pac J Cancer Prev. 2015;16(16):7179-7188.
[49] Yazdanpanahi N, Behbahani M, Yektaeian A. Effect of Boswellia thurifera gum methanol extract on cytotoxicity
and p53 gene expression in human breast cancer cell line. Iran J Pharm Res. 2014;13(2):719-724.
[50] Jaafari-Ashkavandi Z, Hamedi A, Assar S, Ebrahimpour A. The effects of frankincense on oral squamous cell
carcinoma cell line. Int J Cancer Manag. 2017;10(5).
[51] Jones MA, Borun A, Greensmith DJ. Boswellia carterii oleoresin extracts induce caspase- mediated apoptosis and
G1 cell cycle arrest in human leukaemia subtypes. Front Pharmacol. 2023;14:1282239.
[52] Elnawasany S, Haggag YA, Shalaby SM, Soliman NA, El Saadany AA, Ibrahim MAA, Badria F. Anti-cancer effect of
nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line. BMC Complement Med
Ther. 2023;23(1):270.
[53] Li W, Liu J, Fu W, Zheng X, Ren L, Liu S, Wang J, Ji T, Du G. 3-O-acetyl-11-keto-β- boswellic acid exerts anti-tumor
effects in glioblastoma by arresting cell cycle at G2/M phase. J Exp Clin Cancer Res. 2018;37(1):132.
[54] Sharma A, Gupta NK, Dixit VK. Complexation with phosphatidylcholine as a strategy for absorption enhancement
of boswellic acid. Drug Delivery. 2010;17(8):587–595.
[55] Al-Yasiry AR, Kiczorowska B. Frankincense--therapeutic properties. Postepy Hig Med Dosw. 2016;70:380–391.
[56] Lv M, Shao S, Zhang Q, Zhuang X, Qiao T. Acetyl-11-Keto-β-Boswellic Acid Exerts the Anti-Cancer Effects via Cell
Cycle Arrest, Apoptosis Induction and Autophagy Suppression in Non-Small Cell Lung Cancer Cells. OncoTargets
Ther. 2020;13:733–744.
GSC Biological and Pharmaceutical Sciences, 2024, 26(01), 349–362
362
[57] Sharma T, Jana S. Boswellic acids as natural anticancer medicine: Precious gift to humankind. J Herb Med.
2020; 20:100313. ISSN 2210-8033.
[58] Hussain H, Ali I, Wang D, Hakkim FL, Westermann B, Rashan L, et al. Boswellic acids: Privileged structures to
develop lead compounds for anticancer drug discovery. Expert Opin Drug Discov. 2021;16(8):851–867.
[59] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.
[60] Esposito M, Ganesan S, Kang Y. Emerging strategies for treating metastasis. Nature cancer. 2021;2(3):258–270.
[61] Memarzia A, Saadat S, Asgharzadeh F, Behrouz S, Folkerts G, Boskabady MH. Therapeutic effects of medicinal
plants and their constituents on lung cancer, in vitro, in vivo and clinical evidence. J Cell Mol Med. 2023;27:2841-
2863.
[62] Salehi B, Zucca P, Sharifi-Rad M, Pezzani R, Rajabi S, Setzer WN, Varoni EM, Iriti M, Kobarfard F, Sharifi-Rad J.
Phytotherapeutics in cancer invasion and metastasis. Phytotherapy research: PTR. 2018;32(8):1425–1449.
[63] Yadav VR, Prasad S, Sung B, Gelovani JG, Guha S, Krishnan S, Aggarwal BB. Boswellic acid inhibits growth and
metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory,
proliferative, invasive and angiogenic biomarkers. Int J Cancer. 2012;130(9):2176–2184.
[64] Marcuzzi E, Angioni R, Molon B, Calì B. Chemokines and Chemokine Receptors: Orchestrating Tumor
Metastasization. Int J Mol Sci. 2019;20(1):96.
[65] Lazennec G, Richmond A. Chemokines and chemokine receptors: new insights into cancer-related inflammation.
Trends Mol Med. 2010;16(3):133–144.
[66] Schlecht-Louf G, Deback C, Bachelerie F. The Chemokine System in Oncogenic Pathways Driven by Viruses:
Perspectives for Cancer Immunotherapy. Cancers. 2022;14(3):848.
[67] Park B, Sung B, Yadav VR, Cho SG, Liu M, Aggarwal BB. Acetyl-11-keto-β-boswellic acid suppresses invasion of
pancreatic cancer cells through the downregulation of CXCR4 chemokine receptor expression. Int J Cancer.
2011;129(1):23–33.
