Cancer chemoprevention : alternative strategies

Internet Journal of Medical Update, Vol. 2, No. 2, Jul-Dec 2007 Editorial
Cancer chemoprevention: alternative strategies

Theeshan Bahorun and Vidushi S. Neergheen

Department of Biosciences, Faculty of Science, University of Mauritius, Réduit,
Republic of Mauritius

As it stands today, cancer is the second leading
factors, modulation by pharmacological or
death cause in the world. In 2005, out of 58
nutritional means the levels of biotransformation
million deaths worldwide 7.6 million people died
enzymes that promote the elimination of
of cancer. Based on projections, cancer deaths
endogenous and environmental carcinogens and
will continue to rise with an estimated 9 million
reduction of angiogenesis are some proposed
people dying from cancer in 2015, and 11.4
chemopreventive strategies. In this particular
million dying in 2030. Statistical data show that
context, nutrition, particularly the use of diets
men are largely plagued by lung, colon, rectum
containing antioxidants, has been suggested for
and prostate cancer whilst women increasingly
cancer prevention. Epidemiological and
suffer from breast, colon, rectum and stomach
experimental studies highlight the protective
cancer. More than 70% of all cancer deaths occur
roles of a range of dietary phytochemicals more
in low and middle-income countries, where
particularly phenolics for the control and
resources available for prevention, diagnosis and
containment of carcinogenesis. Polyphenols
treatment of cancer are limited or nonexistent.
encompass a wide range of biological,
Whilst current clinical therapies including
pharmacological and medicinal properties. They
radiation, chemotherapy, immunosuppression
comprise the simple phenols, phenolic acids
and surgery are limited (and also costly) as
phenylpropanoids, quinones, flavonoids, tannins
indicated by the high morbidity and mortality
and the less common stilbenes and lignans.
rate from cancer, there is an imperative need for
Flavonoid is a broad class of polyphenols with
new treatment modalities. There has been in the
more than 6000 structures. These compounds
past decades several independent concepts
have been characterized into major groups
related to the carcinogenic process indicating that
consisting of flavones, isoflavones, flavanones,
new intervention strategies can be developed that
flavanonols, flavonols, flavanols, flavan-3,4-
could diminish cancer incidence.
diols and anthocyanidins.
They have been
Chemoprevention is a novel approach
reported for their multiple biological activities
emphasizing on the prevention or delay of
including antioxidant, antibacterial, antiviral,
carcinogenesis by means of pharmacologic,
anticarcinogenic, anti-inflammatory, anti-
biologic, and nutritional intervention. This
thrombotic anti-allergic, immune stimulating,
includes the interference of new drugs with
estrogenic and vasodilatory actions amongst
specific cell cycle elements, oncogene products,
others. Several of these pharmacological effects
growth factors, hormone receptors and
are related to their interaction with several
telomerase activity. Chemoprevention by
enzymes including protein kinases,
targeting key components of the apoptosis
cycloxygenase, lipoxygenase and xanthine
regulatory pathways which include the anti-
oxidase and to their free radical scavenging and
apoptotic Bcl-2 family of proteins, IAPs in
metal chelating properties. These pleiotropic
particular XIAP, cIAP1, cIAP2, survivin, NF-
properties have made phenolic compounds
?B, caspases, tyrosine kinases and key signaling
suitable for cancer chemoprevention that entails
routes (the PI-3K/PKB pathway, the Stat3/5
the use of naturally occurring phytochemicals to
pathway and the MAPK pathway) seems to be a
prevent the onset and/or the progress of
rational approach in reducing the incidence of
carcinogenesis. Flavonoids have been shown to
cancer. Targeting of the tumour
be potent biomodulators at the cellular,
microenvironment, more particularly subcellular and molecular levels and they can act
inflammatory mediators and reactive
as mediators of cell differentiation, apoptosis,
oxygen/nitrogen species, upregulation of gap
protein/enzyme. (-)-Epigallocatechin-3-gallate,
junctional intercellular communication (GJIC),
the major catechin found in tea inhibits cervical
regulation of upstream kinases of intracellular
cancer cell growth in vitro through the regulation
signalling cascades, downstream transcription
of gene expression, cell cycle progression and

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Internet Journal of Medical Update, Vol. 2, No. 2, Jul-Dec 2007 Editorial
apoptosis. Several anthocyanins and phenolic
activity mostly through the antioxidative
acids protect against DNA mutation by
property.
Phenolics including (+)
scavenging free radicals and also by protecting
epigallocatechin gallate, capsaicin, curcumin,
DNA nucleophilic sites. In addition to their free
caffeic acid phenyl ester (CAPE) and resveratrol
radical scavenging properties, some phenolic
have been reported to down-regulate
antioxidants such as genistein act through
proinflammatory mediators e.g TNF-?, IL-8.
enhancing the activity of a number of antioxidant
Moreover the ability of phenolic components to
enzymes, including catalase, glutathione
downregulate the proinflammatory enzymes
peroxidase, glutathione reductase, and
COX and iNOS enhanced their prophylactic
superoxide dismutase therefore maintaining the
potentials in cancer. Several compounds for
genome integrity.
The implication of
example resveratrol, gingerol, CAPE, curcumin,
inflammatory processes and oxidative stress on
EGCG, capsaicin have been reported to mediate
carcinogenesis indicate the therapeutic benefit of
their anti-carcinogenic via COX and iNOS
natural anti-inflammatory agents that exert their
inhibition.




Antiangiogenic and apoptosis inducing effect of
kinase B/Akt, glycogen synthase kinase (GSK).
the polyphenols makes them suitable
This can prevent the aberrant activation of the
chemopreventive In addition antioxidative effect
cellular signaling network, hence reducing
of phytochemicals has recently been linked to
neoplastic transformation. In addition MAP
antiangiogenesis since reduction of oxidative
kinase cascades transmit and amplify signals
stress by polyphenols leads to an altered cellular
involved in apoptosis and flavonoids have
redox state, resulting in a reduced activation of
received considerable attention as signaling
transcription factors such as AP-1, p53 and NF-
molecules. The intricate link between MAPK
?B, which regulate the expression levels of the
activation and inhibition of GJIC has been
key angiogenic factors VEGF. The ability of
widely discussed thus MAPK inhibitors are
phenolic compounds to target protein kinases and
prospective therapeutic compounds against
transcription factors also enhances their
carcinogenesis. Several phenolic constituents
chemopreventive potential. Several phenols
including CAPE, resveratrol, epicatechin,
including curcumin, flavonoids, genistein,
apigenin, tangeretin have been described to
resveratrol, catechins, have been identified to
restore GJIC. The procyanidin B5-3’-gallate has
target enzymes of the signal transduction
been shown to have cancer chemopreventive
pathways including mitogen activated protein
and/or anticarcinogenic effects in mouse skin
kinases (MAPKs), protein kinase C,
two-stage carcinogenesis model. Oligonol, a
phosphatidylinositol-3-kinase (PI3K), protein
catechin rich product derived from the

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Internet Journal of Medical Update, Vol. 2, No. 2, Jul-Dec 2007 Editorial
oligomerization of polyphenols induced
several pluripharmacological compounds have
apoptosis in MCF-7 and MDA-MB 231 human
been reported to act on multiple molecular and
breast cancer cell lines by modulating pro-
cellular targets and such approach is gaining
apoptotic Bcl-2 family proteins and ERK/MAPK
support to fight cancer. It is noteworthy that in
signaling pathway.
spite of growing evidence in support of the
From the above examples and the high number
potential prophylactic use of food plant
of ongoing and completed studies in this research
derivatives and extracts there is still a tendency
area, it is clear that plant derived antioxidants
for a number of scientists, as rightly pointed out
can meaningfully contribute towards the
by Professor Hamblin (Leukemia Research 30
management of the biochemical and
(2006) 649–650) to “back away from the word
physiological features of cancer and oxidative
“natural” for fear of being contaminated by the
stress related disorders. However bioavailability
beards and sandals brigade flogging organic
concerns arises and this can be resolved by future
produce, acupuncture meridians, radio-ionic
clinical trials that in addition will advance our
diagnosis and snake oils of various flavors”. For
understanding of the efficacy and safety of many
sure, there is a mindset to change!
chemopreventive extracts with therapeutic

potential. There now exist clear trends to show

that the mainstream pharmaceutical research is
Dr. Theeshan Bahorun PhD
moving away from single molecule or single
Associate Editor
target approach to combinations and multiple
Email: tbahorun@uom.ac.mu
target approaches. Plant extracts that contain



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