Page 44 - Read Online

Page 6 of 36 Dave et al. J Cancer Metastasis Treat 2020;6:46 I http://dx.doi.org/10.20517/2394-4722.2020.106

Chemopreventive mechanism of resveratrol
Many studies have been published describing the potential chemopreventive effect of resveratrol. In brief,
resveratrol induces apoptosis by interacting with the αVβ3 integrin receptor in the breast cancer cell line
[55]
MCF-7 . The compound inhibits aryl hydrocarbon receptor activity thereby suppressing tumor growth
[56]
[57]
and exhibiting anti-cancer properties . Further, with MCF-7 cells, resveratrol inhibits NF-κB and BCL-2 .
It antagonizes the aryl hydrocarbon receptor, which can relate to carcinogenic and immunosuppressive
[58]
effects in cells . Some studies suggest that resveratrol shows antitumor effects at the level of initiation,
promotion, and progression with prostate cancer cells . As noted above, resveratrol can inhibit COX-1
[59]
and COX-2, enzymes that are involved in tumor progression. With HL-60 cells, phenotypic markers
indicative of reduced proliferation are induced. Also, in the initiation phase of carcinogenesis, resveratrol
[36]
inhibits free radical generation . In human lymphoblast cell lines, resveratrol induces apoptosis through
[60]
p53 activation . It also inhibits COX-2 activity and ribonuclease reductase . With osteosarcoma stem
[62]
[61]
cells, resveratrol inhibits self-renewal, cell viability and tumorigenesis. Mechanically, resveratrol inhibited
JAK2/STAT signaling and suppressed cytokine synthesis, which was consistent with the decline of CD133
[63]
cancer stem cell (CSC) markers . Thus, when evaluated with in vitro models, resveratrol mediates a
variety of effects consistent with antitumor activity.
EPIGALLOCATECHIN-3-GALLATE
Chemical and pharmacological properties
[64]
Tea as a beverage is popularly consumed around the world, second only to water . Consumption of green
tea has been advocated for several health benefits, such as ameliorating cardiovascular risk and prevention
of cancer. It has exhibited various biological properties proven favorable for hepatic function and improved
metabolic profiles [65,66] . Pharmacologically, the polyphenols present in green tea demonstrate properties
that can lead to anti-oxidative, anti-inflammatory, anti-atherosclerosis, anti-hypercholesterolemic and anti-
carcinogenic activities [67,68] .

Active green tea polyphenols include catechins (members of the flavonoid family), like epicatechin (EC),
epicatechin-3-gallate (ECG), epigallocatechin (EGC), and epigallocatechin-3-gallate (EGCG). ECG
and EGCG are found in the high concentrations (50 to 80% of the catechins) [64,69] . EGCG is the ester of
epigallocatechin and gallic acid and known to be the most potent catechin in exhibiting anti-cancer and
antioxidant effects. The hydroxyl group on the B-ring plays an important role in antioxidant reactions and
[70]
this is increased by the trihydroxyl group on the D-ring .

Inflammation is one dominant factor in the initiation of cancer. Increased oxidative stress promotes cell
growth. Many in vitro studies and studies with animal models have conclusively demonstrated the potential
of green tea to reduce tumorigenesis, although clinical trials are still not definitive. EGCG is hydrolyzed
to EGC in the intestine by bacteria. Later, EGC and gallic acid undergo several conversions leading to
metabolites such as 5-(3,5-dihydroxyphenyl)-4-hydroxyvaleric acid and 5-(3′,5′-dihydroxyphenyl)-γ-
[71]
valerolactone in glucuronide forms . In a clinical study, the plasma levels were 0.17 µmol/L after having 2
[66]
cups of tea, while the in vitro concentrations used in many studies have been in the range of 10-100 µmol/L .
Epidemiological studies have suggested green tea has a positive effect on cancer prevention in certain types
of cancer, namely breast, colon, and skin [72-74] . Although there is lesser or no positive clinical effect seen
with other types of gastrointestinal or oral cancers, there is bactericidal activity against Escherichia coli,
Streptococcus salivarius, and Streptococcus mutans [75-77] .

Chemoprevention mechanism of EGCG
Since it has been established that cancer stem cells play a vital role in tumor progression, studies have
been performed with lung CSCs such as A549 and H1299 illustrating the potential of EGCG to suppress
[78]
tumor formation through the Wnt-β-catenin pathway . Other studies performed with chemotherapeutic