Download PHYTOCHEMICALS – ON CANCER PREVENTION Mechanics and

PHYTOCHEMICALS – ON CANCER PREVENTION
Mechanics and Actions of Phytochemicals on
Cancer Prevention
Janelle Craig, Adrianna Mitchell, Marissa Duvall,
Kirby Davis, Oula Diab and Nikki Cheong
HSCI 441
Dr. Chen
Due December 4, 2014
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Abstract
The value of cancer prevention research is becoming just as valuable as continuing research for
Western accepted cancer treatments due to poor outcome of late-stage cancers. Several
epidemiological studies have identified nutrition is correlated with disease risk, and therefore
have found the value in developing preventive interventions to reduce cases of carcinogenesis.
Dietary phytochemicals has been recognized as a dietary preventive agent for cancers due to its
antioxidant, anti-inflammatory, and pro-apoptotic biological mechanisms and proficient actions
on cancer target cells. However, limitations of phytochemicals have been seen in later stages of
cancer and their modulators have reduced or regressive actions on advance stages of cancer. The
beneficial mechanisms and actions of dietary phytochemicals is discussed and sponsored by an
assortment of studies supporting phytochemicals have mechanisms, biologically and chemically,
whose actions are preventive effectors and can synergistically inhibit the biological process of
carcinogenesis. Further study is essential to bridge the gap between theory and research, and
clinical application.
Keywords: phytochemicals, mechanisms, actions, dietary, cancer, prevention
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Mechanisms and Actions of Phytochemicals on Cancer Prevention
Incidences of cancer are steadily increasing and are among the leading causes of death in
Western society. The cost of cancer therapies and the aggressive behavior of cancer in the later
stages have led scientists to focus on the preventive abilities of cancer preventive dietary agents,
such as, phytochemicals. Furthermore, studies have identified the current population is more
knowledgeable about the disease preventive abilities of dietary nutrients, and desire to prevent
and reduce the unfavorable or debilitating side effects of current Western cancer therapies,
therefore, concluding, the study of phytochemicals has a more of an audience then just in the
clinical setting (Baliga, Thilakchand, Sunitha et al., 2013).
As in the population, the popularity of studying more natural methods has increased due
to the connection between dietary habits, lifestyle and cancer (Westergaard, Jun, Jensen et al.,
2014). Several studies have focused specific fruits and vegetables and their broad synergistic
role in cancer prevention, while other studies have focused on phytochemicals and their roles in
specific-tissue cancers.
For example, several studies focused on prostate cancer and how phytochemicals inhibit
carcinogenic growth since prostate cancer is the second most common cancer among men.
Clinical prostate cancer incidence by nation shows variability due to the consumption of the
Western diet. Epidemiological studies concluded Western nations tend to have a high incidence
of prostate cancer compared to Asian nations who show a lower incident rate. In the USA,
prostate cancer is predicted to account for about 28% of all male cancer diagnoses in 2012. The
rate in Asian nations can be up to tenfold lower. Diet and lifestyle are thought to be the main
contributory factors between the two nations with Asian nations tending to consume much higher
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amounts of cruciferous vegetables than Western nations. Consuming cruciferous vegetable,
which contains glucosinolates, is effective in inhibiting carcinogenic growth (Watson, Beaver,
Williams et al., 2013).
Liver and colon cancer was also exclusively studied and past research indicated that
carotenoid-based phytochemicals is effective to prevent liver cancer. Current phytochemicals
studied are Myo-inositol, which inhibit neoplasia, and Green tea polyphenols (GTPs), which
reduce the tumor formed. Additional studies focused on edible and non-edible plants whose
contributing phytochemicals defense factors were correlated with target proteins on cancer cells
(Westergaard, 2014).
Cell stages in cancer development
Cancer prevention and inhibition can occur at several stages of a cell’s life, and therefore
to understand the broad category of cancer prevention and apply it to a specific dietary therapy, it
is important to understand the process of carcinogenesis.
Carcinogenesis begins with a normal cell in a mammalian model. This normal cell is first
influenced by a carcinogen or infectious agent and is infected. Once this occurs, the normal cell
will enter the cancer-forming process. The first stage of cancer is initiation, is when the infected
cell begins cell proliferation and genome instability follows. Stage three, the promotion stage, is
identified when the mutated cell becomes more vulnerable and is more susceptible by its
promoters to give rise to further cell proliferation. In the promotion stage, replicative immortality
and cell metabolism alteration occurs. Lastly, the mutated cell will go into its last step called
progression. During the progressive stage of cancer there will be cell death evasion,
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inflammation, immune evasion, angiogenesis, and invasion and metastasis (Ki Won, Bode, &
Zigang, D., 2011).
It is these three stages that establish the purpose for studying phytochemicals from three
perspectives – for prevention, in regression and for its synergistic abilities; this is the hallmark of
phytochemical-specific cancer research, and is briefly discussed and applied as the fundamental
outline of this research paper. Overall, The mechanisms and actions of dietary phytochemicals,
biologically, and chemically, have preventive effects, as well as inhibit certain cancers and
various cell functions.
Supporting Research
Cancer Research
The study of dietary phytochemicals have grown in the last decade and has accelerated
our understanding of their chemical and biological functions and how their oral intake can
prevent, reduce malignancy and prevent reoccurrences (Lee, Khor, Shu, et al., 2014). Cancer
prevention research has been categorized into three different categories. The first main type is
primary, which deals with the avoidance of carcinogens. The second type is secondary, where
detection and elimination of premalignant lesions occur. Lastly, the third main type comprises of
preventing cancer reoccurrence, tumor progression, and disease-related complications. These
three categories describe the different aspects of cancer initiation to progression. Phytochemicals’
mechanisms and actions are able to contribute by acting on these separate stages of cancer
prevention in a non-evasive manner, unlike some current cancer therapeutic drugs (Lee et al.,
2014). In other words, phytochemicals can influence the carcinogenic process from tumor
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initiation through the hallmarks of cancer (González-Vallinas, González-Castejón, RodríguezCasado, et al., 2013).
Phytochemical’s mechanisms and actions
Phytochemicals have multiple molecular targets and are capable of interfering in every
stage of cancer development comprising of cell proliferation, apoptosis, invasion and metastasis,
angiogenesis, immortality, inflammation, immunity, genome instability and mutation, and cell
energetics and metabolism (González-Vallinas et al., 2013). These capabilities make them a
very efficient dietary compound in cancer prevention.
The different stages of the cancer process along with several inhibiting factors of phytochemicals
are shown in Figure 1.
Figure 1. Stages of cancer process inhibited by phytochemicals. Illustrated is an example of how
phytochemicals can interfere with any stage of cancer development.
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Inhibiting Carcinogenesis
Phytochemical’s mechanisms and actions. Several studies have been conducted and prove
phytochemicals have the ability to inhibit the initiation of a variety of cancer cells. However,
several studies identified cancer therapies in the late stage of the disease remain to have an
overall poor efficiency. Many argue that there should be a shift from cancer therapies to avoid
poor outcomes and focus more so on cancer prevention (Ki Won et al., 2011). Research has been
done to see what phytochemical mechanisms can inhibit carcinogenesis, and, if possible, impede
multiple targets at once to prevent cancer.
Several studies that proved phytochemicals benefit, conducted further analyses of DNA
and protein-antibody arrays and identified phytochemicals have a unique DNA and protein
expression (Nishino, 2009). These protein expressions are responsible for the phytochemical’s
ability to directly scavenge free radicals and signal via the nuclear factor erythyroid-2 (NF-E2)
and a protein complex to induce cell defense mechanism to detoxify (known as phase II) and
transport anti-oxidative stress proteins (phase III transporters) to protect the cell from the
initiation of carcinogenesis. Furthermore, growth inhibitors found in phytochemical could
activate cytochrome c and induce apoptosis in pre-neoplastic cells. These are cells that have not
metastasized yet (Lee et al., 2014).
One study identified dietary phytochemicals as preventive agents in terms of modulating
cell signaling pathways. The preventive agents are know to inhibit mutations of Mitogenactivated protein kinases (MAPK) pathway (a chain of proteins in the cell that communicates a
signal from a receptor on the surface of the cell to DNA); the oncogenic AKT pathway (pathway
in cell signaling blocking apoptosis and leading to cell survival); and proteins involved with cell
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cycle progression (protein kinase B (PKB) and phosphoinositide 3-kinase (PI3K) (Ki Won, Bode,
& Zigang, 2011).
The first concept is how phytochemicals interfere with the MAPK signaling pathways.
Phytochemicals are able to do so by acting as an inhibitor of the proliferating protein, MEK1.
MEK1 is a key component to the oncogenic RAS signaling, making it a good target to disrupt the
MAPK pathway. In this case, phytochemicals, such as quercetin, myricetin, and equol, are able
to bind to the allosteric site to ultimately affect the binding affinity of a compound with a target
protein (Ki Won, Bode, & Zigang, 2011).
The carcinogenic inhibiting properties of glucosinolate. Several studies, more specifically,
identified glucosinolates, found in cruciferous vegetables, as having carcinogenic inhibiting
properties via cytotoxic activity. Several types of cruciferous vegetables that contain this
phytochemical give rise to other bioactive species include broccoli, cauliflower, and Brussels
sprouts. These crucifers are the most common in the Western diet. Additional crucifers that
contain glucosinolates are daikon, watercress and bock Choy, which are more common in the
Asian diet than they are in the Western diet. Glucosinolates are cleaved by the plant enzyme
myrosinase when chewed in the mouth to yield active phytochemicals that influence varying
degrees of anti-cancer activity (Watson et al., 2013).
In the article, Phytochemicals from Cruciferous Vegetables, Epigenetics, and Prostate
Cancer Prevention, the ability of these phytochemicals to inhibit prostate cancer and suppress
activity is discussed through multiple tests. Studies have attributed this activity to the metabolic
products glucosinolates, a class secondary metabolite produced by the above-mentioned crucifers.
In particular, the metabolic products glucoraphanin, glucobrassicin, sulforaphane, and indole-3-
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carbinol (I3C) have been under extreme investigation by cancer researchers due to their ability to
stimulate NF-E2 and control gene expression and decrease Akt signaling in prostate tissue
(Watson et al., 2013).
When Glucosinolates are cleaved by myrosinases during chewing, sulforaphane and I3C
are released from their precursors. Sulforaphane undergoes enzymatic metabolism through the
mercapturic acid pathway and I3C undergoes spontaneous self-condensation and polymerization
in the gut. Sulforaphane and its metabolites are the principal bioactive phytochemicals derived
from broccoli and broccoli sprouts. Sulforaphane is present as the glucosinolate glucoraphanin.
Glucoraphanin is cleaved by myrosinase into sulforaphane and glucose. Once it is released,
Sulforaphane can be taken up by the human gut and then metabolized through the mercapturic
acid pathway. This produces several metabolic products (Watson et al., 2013).
Post-consumption products are produced that possess anti-cancer activity including
reducing gene expression related to: Transforming Growth Factor beta (TGFB) (acts as a
transcription factor in the nucleus and participates in the regulation of target gene expression);
insulin signaling; and mutagenic Epidermal growth factor (EGF) signaling. The Mercapturic acid
pathway produces condensed products when formed from the coupling of cysteine with
compounds, such as, I3C and will eventually excrete mutagenic-causing compounds in the urine
(Watson et al., 2013).
One product is diindolymethane (DIM). DIM is produced when I3C is released from the
precursor glucobrassicin by the enzyme myrosinase in the acidic environment of the stomach.
Glucobrassicin is found in high concentration in a variety of cruciferous vegetables, such as,
Brussels sprouts and garden cress. In the stomach, I3C is quickly converted into an assortment of
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acid condensation products and modified derivatives. Several experiments, where I3C was orally
administration to subjects, provided evidence that diindolymethane (DIM) was the only acid
condensation product detected in plasma and was responsible for decreasing cell markers and
increasing cell death effectors (Watson et al., 2013). DIM’s actions are possible by a mechanism
distinct from other radioprotectors and mitigators involving stimulation of the DNA damage
response, including DNA repair, and activation of cell survival signaling through the
transcription factor NF-κB (Shukla, Meeran, & Katiyar, 2014). This data supports DIM as the
key mediator of cancer protection, specifically in prostate cancer (Watson et al., 2013).
Carotenoid Cocktail in Cancer Prevention. Liver cancer patients have been treated using
interferon, and clinical report identify many patients do not respond to this type of therapy. A
research study performed at Kyoto Prefectural University of Medicine and Ritsumeikan
University in Japan evaluated the methodology of treating liver cancer in hepatitis virus infected
patients using a combination of carotenoid-based phytochemicals (Nishino, 2009).
A study by Kyoto Prefectural University of Medicine and Ritsumeikan University in
Japan reviewed the inhibition of phytochemicals alpha/beta carotene, Lycopene, Zeaxanthin,
Myo-Inositol and Glycyrrhizin on spontaneous liver carcinogenesis and their ability to suppress
tumorgenesis in various organs. Results identified lycopene, zeaxanthin and myo-inositol
(phytate) inhibited hepatomas more than alpha/beta-carotenes (Table 1). Myo-inositol, the
greatest inhibitor, inhibits neoplasia by dephosphorylated products not only in the liver, but also
in the mammary glands, colon, lung and stomach (Nishino, 2009).
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Table 1. Effects of phytochemicals on spontaneous liver carcinogenesis in C3H/HE. Table
identifies the percentage of inhibition on carcinogenic liver cells.
Suppression of Cancer Cells
Phytochemicals (Polyphenols) and DNA suppression. Phytochemicals have been shown to
stop or reduce tumor growth once formed. One study identified dietary phytochemicals as
suppressing agents in terms of modulating cell signaling pathways and has been shown to be
efficient in suppressing AKT signaling, identified to obstruct apoptosis. AKT and Mechanistic
Target of Rapamycin (mTOR), a serine/threonine protein kinase that regulates cell functions as
an immunosuppressant, are involved in the reprogramming of the metabolic pathways in cancer
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cells. The AKT-mediated oncogenic pathway is believed to be regulated by nutrients.
Phosphatidylinositol 3-kinase (PI3K), another oncogenic factor, is also a regulator of AKT and
mTOR signaling in which also interacts with phytochemicals. Phytochemicals are able to
suppress the activity of PI3K, which ultimately suppresses the AKT-mediated oncogenic
pathway (Ki Won et al., 2011).
Several factors have been identified to be large contributors to the mediation of cancer;
one being, epigenetics. Epigenetics are a genetically inherited form of gene expression that
doesn't change DNA sequencing, and are required for growth and gene expression. Epigenetic
disruptions are caused by hypermethylation, histone modification and altered microRNA, which
promote gene silencing in cancer cells, deactivating transcription of genes, and induce
degradation of translation of target messenger RNA, respectively. Mechanisms for epigenetic
disruptions include use of dietary phytochemicals, physical activity, infections and several other
environmental factors (Lee et al., 2014).
Dietary phytochemicals have been reported to regulate these epigenetic disruptors and
restoring normal gene expression. Green tea polyphenols (GTPs) including epigallactin-3-gallate
(ECGC) decreased DNA methylation, and caused re-expression of the mRNA and proteins of
previously silenced tumor suppressor genes. This is especially critical, since the mutations
caused by epigenetics prevents cells from scavenging for free radicals via NF-E2 and signaling
for acceleration of defense mechanisms against carcinogenic growth (Lee et al., 2014).
Carcinogenic suppression properties of glucosinolate products. Sulforaphane and DIM,
found in cruciferous vegetables, are also able to suppress cancer growth by inhibiting growth and
stimulating apoptosis of transformed cells. This suggests sulforaphane and DIM have activity
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outside of phase I and phase II response. Recent investigations have attributed suppressive
activity to antagonism of signaling pathways known to be important for prostate cancer
progression. For example, the AKT signaling axis and modulation of epigenetic enzymes are
responsible for contributing growth prevention and initiation of apoptosis (Watson et al., 2013).
Dietary Isothiocyanates (ITCs) are bioactive hydrolysis products that are derived from
many cruciferous vegetables. Expansive evidence from cell and animal models indicates several
molecular mechanisms of chemoprevention and suppression by ITC’s. This includes modulation
of phase I, II, and III detoxification, regulation of cell growth by induction of apoptosis and cell
cycle arrest, induction of ROS mechanisms, and regulation of androgen receptor pathways
(Melchini, Traka, Catania et al., 2013).
In the article, Antiproliferative Activiety of the Dietary Isothiocyanate Erucin, a Bioactive
Compound from Cruciferous Vegetables, on Human Prostate Cancer Cells, Erucin (ER), a
dietary ITC was examined as a promising cancer preventive and suppression phytochemical. ER
was investigated using prostate adenocarcinoma cells (PC3) to analyze its effects on pathways
involved in cell growth regulation. The effect of ER on human prostate cells was compared to
similar sulforaphane (SF) treatment (Melchini et al., 2013).
The results of this experiment indicate ITC’s show a strong antiproliferative effect at
higher concentrations and an increase in cell numbers at lower concentrations. At low
concentrations of both ITC’s (SF and ER) there was an arrested state of PC3 cells. SF appears to
be a more potent inhibitor. It reduced cell PC3 cell proliferation by 80%. Both ITC’s appear to
be able to arrest cell proliferation at concentrations as high as 75 mm. the results also showed ER
and SF significantly enhanced the expression levels of p21 in cancerous PC3 cells. The highest
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concentration of both ITC’s caused an increase of p21 level of more than twofold compared to
the level in untreated cancer cells (Melchini et al., 2013).
It is becoming progressively evident that ITC’s can delay or prevent the process of
prostate cancer by multiple mechanisms. This study identified ER is able to significantly reduce
the viability and proliferation activity of adenocarcinoma prostate PC3 cells and is able to do so
without affecting AKT cell phosphorylation (Melchini et al., 2013).
Phytochemical restoration abilities. Phytochemicals have the ability to restore aberrant
epigenetic alterations with anti-cancer mechanisms. One study conducted a clinical trial on the
phytochemical, lycopene, and analyzed the development of hepatocellular carcinoma over a two
to five year timespan. Half of the subjects were give 4 capsules daily (20 mg) containing
lycopene, beta-carotene, alpha carotene, other carotenoids (photogene and phytofluene), and
alpha tocopherol. After the intervention, results showed more than 50% suppression in
hepatocellular carcinoma after the fourth year in the treated group compared to the control group
(Nishino, 2009).
Furthermore, an additional research study presented mandarin orange juice, enriched with
beta cryptoxanthin and myo-inositol, and carotenoids capsule to liver cancer patients with
cirrhosis and hepatitis. Results concluded hepatocellular carcinoma inhibition of 81% after 2.5
years of the intervention. Further DNA-array analysis of Beta-cryptoxanthin identified critical
levels of induced gene expression on cell cycle control genes of p16 and p73 also known as
tumor suppression genes. DNA and protein-antibody arrays identified each phytochemical
express specific proteins and self-specific DNA (Nishino, 2009). Combination of multiple
phytochemicals is important to obtain the desired results of prevention liver cancer.
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Human proteins and phytochemical interaction. A research study performed in by the
University of Hong Kong, studied the relation between dietary phytochemicals and colon cancer
progression. One hundred and fifty-eight plants were studied to identify the relationship between
produced phytochemical defense factors and mechanisms of action, and “candidates,” the
proteins that are associated with colon cancer. The 158 plants have 3,526 unique phytochemicals
and were compared to the ChMEBL, which is a large repository that provides data for chemicalprotein interactions. This study found that 1,663 of plants’ phytochemicals have direct
interactions with humans’ proteins. Furthermore, it identified each plant interact with a certain
number of target proteins involved in colon cancer (Westergaard et al., 2014).
The most targeted protein by edible plants was Epidermal Growth Factor Receptor
(EGFR) with 79%. When focusing on the KEGG colon cancer pathway (a signaling pathway
that maps for 14 cancers), 11 edible plants were found to have similar compounds targeting three
proteins (MARK1, SMAD3, and GSK3B). Edible plants included black tea, which had 5
molecules and 7 target proteins, and ginger had 4 small molecules and 5 target proteins.
Furthermore, the study identified the phytochemicals’ target proteins by colon cancer cells and
identified luteolin, a compound found in those 11 edible plants, had an interaction network with
15 proteins from the three identified candidate colon cancer target spaces mentioned above. The
second most correlated phytochemical target protein was rutin, which was found in 19 edible and
was associated with the two carcinogenic target proteins, NT5E and EGFR. Plant varieties and
target proteins are identified in Table 2 (Westergaard et al., 2014).
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Table 2. Edible and Non-edible plants, compounds, and carcinogenic target proteins.
This research concluded out of the 3060 reactions of the colon metabolic network, plants
affect 570 reactions with the most targeted parts of the colon metabolic network being the lipid,
fatty acid, pyruvate metabolism, and the TCA cycle. Several types of cancer are associated with
changes in lipid metabolism and fatty acid biosynthesis and are associated with a significant
reduction in citrate concentration and down-regulation of the pyruvate dehydrogenase, a control
step of the TCA cycle. Phytochemicals work as substrates in all of these metabolic reactions and
act in a reverse action in comparison to the tumor related reactions (Westergaard et al., 2014).
Synergistic collaboration of Phytochemicals
Cancer Stem Cells. Phytochemicals not only have critical chemoprevention and suppression
mechanisms and actions, but also are able to intervene with cell cycle progression and reverse
metastasis of cancer cells. Cell cycle progression is dependent on essential proteins known as
cyclin-dependent kinases and inhibiting cyclin-dependent kinases blocks residual cell cycle
progression (Ki Won et al., 2011).
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There are several phytochemicals that act as cyclin-dependent kinase inhibitors, which
will regulate cancer cell proliferation (Ki Won et al., 2011). Figure 2 displays the several
different oncogenic signaling pathways that were discussed above.
Figure 3 Representative oncogenic pathways. This illustration displays how different activations
of signaling effectors can lead to cell cycle progression in cancer cells.
Cited Source: (Ki Won et al., 2011). Representative oncogenic pathways. Illustration diagram.
Nature Reviews Cancer, 11(3). p.215. Retrieved October 21, 2014 from Academic Search
Premier database.
Cell cycle progression in cancers cells is supported by the Cancer Stem Cell (CSC)
theory. Cancer cells are known to have the ability to self-repair, differentiate, maintain growth
and potentially multiply within a malignant tumor. Oxidative stress and inflammation causes
damage by carcinogenetic environmental contaminants causing oncogenic sporadic propagation,
epigenetic alterations and progression into CSCs. However, phytochemicals, such as EGCG and
sulforaphane, have mechanisms with the ability to decrease cancer cell survival by decreasing
gene expression (Lee et al., 2014).
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In normal tissues, stem cells self-renew and differentiate in coordination with common
adjacent cells. However, oxidative stress can cause mutation in cell signaling and create
tumorigenic proliferation. The concern with CSC’s is that they are more resistant to conventional
therapeutic treatments and chemoprevention, and phytochemical collaboration is necessary to
overcome cancer progression (Lee et al., 2014).
Synergistic intracellular events. In relation to the mechanisms of dietary phytochemicals the
pose a single biological response on oncogenic pathways, chemo preventative activity of
phytochemicals are also observed to have a combination of intracellular events. These
mechanisms can be divided into three different aspects, which include antioxidant activity, antiinflammatory activity, and induction of apoptosis (Tan, Konczak, Sze et al., 2011).
Antioxidant, anti-inflammatory, and pro-apoptotic activity are three representative
aspects that are significant pathways that act in preventing, suppressing, or even reversing the
development of carcinogenesis when phytochemicals work cohesively. Screening for dietary
phytochemicals that possess these characteristics can ultimately affect the process of
chemoprevention (Tan et al., 2011).
Recent studies have suggested that the health benefits of dietary phytochemicals are due
to the synergistic interactions of the most active ginger extract (GE) biophenolics. In the article,
Ginger Phytochemicals Exhibit Synergy to Inhibit Prostate Cancer Cell Proliferation, GE
biophenolics is most active in antiproliferative efficacy when acting as a single agent and in
binary combinations on cancer prostate cancer cell line (PC3). PC3 cells are useful in
investigating and assessing the biochemical alterations in advanced prostatic cancer cells. The
nature of their interactions is also investigated using the Chou-Talalay combination index (CI)
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method, the most accurate for combinational drug studies. It considers exclusive and
nonexclusive drugs in addition to sigmoidal and hyperbolic dose effect curves due to increase in
affinity (Brahmbhatt, Gundala, Asif, et al., 2013).
Ginger is one of the most frequently consumed dietary agents. It is widely used for
digestive disruptions including diarrhea, vomiting, nausea, gastritis and colic. The main bioactive
constituents of ginger extract are 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol. This study,
a first of its kind, highlighted the relationship between DRI-level doses, and synergistic amounts
of phytochemicals found in GE. The study substantiated the claim that ginger phytochemicals are
more potent than ginger extracts, 6-gingerol is the most abundant phytochemical in ginger
extract and the combination of ginger biophenolics and constituents exhibited an enhancement in
antiproliferative activity then when consumed singularly (Brahmbhatt et al., 2013). Furthermore,
ginger phytochemicals’ synergistic relationship is responsible for their heightened efficiency at
lower dose levels when present in ginger extract.
Holy Basil role in chemoprevention and radioprotection. Ocimum sanctum L., also known as
Holy Basil or Tulsi, is used in India as a natural remedy for cancer. Its phytochemicals, eugenol,
rosmarininc acid, apigenin, myretenal, luteolin, B-sitosterol and carnosic acid, have protective
effects against carcinogenic cell growth, and chemicals and radiations that induce skin
carcinogens, such as 7,12-Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol13-acetate (TPA). DMBA is a laboratory-specific carcinogen used as a tumor initiator and
immune suppressor. Tumor rate acceleration is induced with treatments of 12-Otetradecanoylphorbol-13-acetate (TPA) on order to expedite tumor proliferation in research
studies (Baliga et al., 2013).
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The protection process of these phytochemicals occurs using different mechanisms such
as decreasing oxidative stress and inflammation and promoting apoptosis. Ocimum sanctum’s
extract is also used to treat lung cancer by inducing apoptosis and reducing the growth of lung
cancerous cells. For example, carnosic and rosmarinic acids in Tulsi have the ability to stop the
growth of lung cancer cells called NCI-H82. In addition, luteolin has the ability to suppress the
growth and metastasis of lung cancer cells called A549 (Baliga et al., 2013).
Regarding breast cancer, Tulsi’s phytochemical, eugenol, inhibits cell growth and
proliferation, and luteolin promotes cancerous cells death by regulating estrogen signaling, and
suppressing development and survival of breast cancerous cells (Baliga et al., 2013).
With all the phytochemicals that the Tulsi plant possesses, it has a massive protection
effect against different types of cancers. This protection has been achieved mainly because of the
phytochemicals’ role as antioxidants and the anti-mutagenic role against cancerous cells (Baliga
et al., 2013).
Discussion
Currently, cancer is one of the leading causes of death in the world. Billions of dollars are
spent each year in hopes of finding cures, key preventive agents or better therapies. According to
the Westergaard et al. (2014) article exploring mechanisms through molecular interaction
networks, the study supports phytochemicals play a pivotal role in the overall quality of life and
is the reason for further research on mechanisms and actions of phytochemicals (Westergaard et
al., 2014).
Current research identifies phytochemicals are chemicals that are found in edible and
non-edible plant sources. Even though, they may not have any nutritive value, they are
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recognized as substrates that work in several metabolic reaction, including as modulators of
major cell-signaling pathways that have proven anticancer effects (González-Vallinas, et al.,
2013).
Extensive years of research have established phytochemicals as being beneficial effecters
on cancer prevention, inhibition and progression. For example, Watson et al.(2013), supported
previous studies that cruciferous vegetables have beneficial synergistic inhibitions on prostate
caner due to the plethora of encompassing phytochemicals, such as glucosinolates, its derivatives
and DIM producing IC3. Their ability to promote apoptosis and control gene expression are key
actions of the glucosinolate’s derivatives, which is critical in stagnating and preventing prostate
cancer. These are critical abilities since prostate cancer is a leading cause of cancer among men
worldwide, with Western nations tending to have higher incidences of prostate cancer compared
to Asian nations. Diet and lifestyle were to blame (Watson et al., 2013).
Phytochemicals have proven to be more efficient on anti-tumor effects in the body when
targeted synergistically. In the article, Ginger Phytochemicals Exhibit Synergy to Inhibit Prostate
Cancer Cell Proliferation, by Tan et al. (2011) phytochemicals cell modulators work more
efficiently when working cohesively and have a greater impact against multiple targets, rather
than working specifically. This article also emphasized the three important and significant
actions have shown to inhibit tumor development: Anti-oxidation, anti-inflammation, and
apoptotic actions (Tan et al., 2011). Even though more research is needed, it is recognized as a
significant development in the actions against cancer promotion and progression. Another
phytochemical is called Erucin (ER) and works as a cancer suppressor and cell regulator to
prevent cancer cell growth (Brahmbatt et al., 2013). In addition, ginger contains ginger extract
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(GE), which is also effective to interfere with cancer cell replication. Consuming cruciferous
vegetable, which contains glucosinolates, is effective in inhibiting carcinogenic growth
(Melchini et al., 2013).
Research also indicated there was a variety of carotenoid-based phytochemicals effective
in preventing liver cancer. Myo-inositol is known to inhibit the neoplasia in the liver, and works
as a suppressing agent in the mammary glands, colon, lung and stomach. Another suppressing
agent is Green tea polyphenols and is able to inhibit or reduce the tumor formed. Another
experiment showed people who consume carotenoids daily have 50% suppression in
hepatocellular carcinoma. Mandarin orange juice, which is very effective with patients with
cirrhosis and hepatitis, showed an 81% suppression in the hepatocellular carcinoma. From these
evidences proved that carotenoid-based phytochemical is effective to suppress the cancer cell
and prevent the liver cancer (Nishino, 2009).
Lastly, studies observed there are a total of 11 edible plants that contain luteolin, found in
black tea and ginger, and 19 edible plants contain rutin, found in strawberry; all of them effective
in preventing colon cancer (Westergaard et al., 2014). Holy Basil or Tulsi, is one of the plants
that are used in the Indian Continent as a natural remedy for cancer, especially skin cancer and
breast cancer (Baliga et al., 2013).
Conclusion
In conclusion, the mechanisms and actions of dietary phytochemicals have the ability to
interfere with cancer development, such as the apoptosis, cell proliferation, and metastasis.
Different dietary nutrients have different varieties of phytochemicals to prevent cancer or
suppress cancer cells. Phytochemicals can also influence the cell replication, DNA repairing,
PHYTOCHEMICALS – ON CANCER PREVENTION
23
tumor formation, gene expression, tissue signaling, enzyme regulation, and cancer cell regulation,
etc. Lastly, synergistically, phytochemicals can prevent a variety of different cancers
(Westergaard et al., 2014; Baliga et al., 2013; & Lee et al.,2013).
Phytochemicals are identified as key cell effectors in cancer prevention, and have shown,
on a smaller scale, to be advantageous at later stages, whether it is at initiation, or during
progression of carcinogenesis. The reason why phytochemicals have more of an affect in
prevention and less of an affect in inhibiting or regression of further cancer proliferation is
statistically unclear and further research is necessary (González-Vallinas et al., 2013). Lee et al.
(2013) further identified further advancements are necessary in detections tools of tumorigenesis,,
since in the earlier stages, cancer is asymptomatic (Lee et al., 2013).
Currently, a high percentage of research prove phytochemicals have a substantial affect
on cancer prevention, and future studies will need to specifically emphasize studying molecular
targets in cell activity and in the body from the perspective of stagnation and regression of
carcinoma proliferation (González-Vallinas et al., 2013).
There are thousands of plants with potential cancer inhibiting phytochemicals and a
majority of them have not been studied for their biological activity of protein targeting. More
advance nutritional interventions are key to more influential and accepted dietary-based
intervention to prevent cancer (Westergaard et al., 2014).
.
24
PHYTOCHEMICALS – ON CANCER PREVENTION
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