1. Cervical Cancer!
• The second most common cancer worldwide"
• Major threat to women"
• Human papillomaviruses (HPV) have been identified as
the major causative factor in cervical carcinogenesis"
• Low-risk (LR-HPV) and high-risk (HR-HPV) classification
depends on the HPV-associated lesions that undergo
malignant progression"
• Oxidative stress is another causative agent in the
development of cervical cancer, its increase is associated
with DNA damage and rapid malignant progression "
Antioxidants!
• Any substance that, when present in low concentrations,
significantly delays or inhibits the oxidation of a specific
substrate"
• Prevent damage to cellular components caused by free
radicals"
• Free radical damage is associated with the development
of cervical cancer"
• May aid to prevent cell damage and progression of
cervical carcinogenesis"
• Polyphenols are naturally occurring antioxidants, mainly
found in citrus fruits, green tea extracts, berries, nuts, and
turmeric plants"
• Promising agents towards the treatment of cervical cancer"
• Known for their induction of apoptosis, ability to arrest growth,
modulate the signal transduction pathways, inhibit DNA synthesis"
• Aid in the prevention of cancer by interfering with the initiation,
promotion, and progression of carcinogenesis"
• Studies have determined that polyphenols can selectivity inhibit
abnormal cell growth, and are therefore a favorable therapeutic
pathway for cervical cancer treatment"
• Treatments of polyphenol extractions have shown to inhibit the
growth of cervical cancer cells, as well as trigger apoptosis in
cancer cells that are in G2/M phase"
• Effective inhibitors of cancer cell proliferation and the focus of
future cervical cancer therapy research"
Curcumin!
• Natural polyphenolic compound extracted from turmeric plants"
• Suppresses all 3 stages of carcinogenesis: initiation, promotion,
progression"
• Known to sensitize cervical cancer cells during therapeutic studies
of taxol"
Ferulic Acid!
• Occurs in seeds and leaves of rice, wheat, oat, tomatoes, coffee,
citrus fruits"
• Inhibits anti-apoptotic proteins and induces apoptosis"
EGCG (Epigallocatechin gallate)!
• Polyphenolic compound found within green tea"
• Threshold levels induce apoptosis and growth inhibition in cancer
cells"
• Inhibits angiogenesis, a key step in the progression of cervical
cancer"
• Inhibits telomerase activity required for the initiation and
progression of cervical lesions"
Resveratrol!
• Found in nuts, berries, grapes, and red wine"
• Inhibits cellular activity associated with the initiation, promotion,
and progression of cervical cancer cell line growth"
• The condition of oxidative stress arises from an increased
production of reactive oxygen species (ROS) associated
with decreased antioxidant capability within the cell"
• Generated during the incomplete reduction of O2 to H2O,
inflammations, infections, mechanical and chemical
stresses, and with the exposure to UV and ionizing
irradiation"
• Increased ROS production rates occur in highly
proliferative cancer cells due to the presence of oncogenic
mutations "
• Vitamin C, a classical indicator of oxidative stress, has
been proven through a study to reduce cancer risk by
providing a degree of protection for DNA from damage by
ROS. Patients showed an increase in oxidative stress levels
due to their diminished vitamin C levels"
• Increased lipid peroxidation, the process in which free
radicals are formed, has a positive correlation with the
depletion of vitamin C"
• Studies show that patients with cervical carcinogenesis
tend to have high levels of oxidative DNA damage and rapid
malignant progression"
• Zhu, X.; Wang, J.; Ou, Y.; Han, W.; Li, H. Polyphenols extract of Phyllanthus emblica
(PEEP) induces inhibition of cell proliferation and triggers apoptosis in cervical cancer cells.
Eur J Med Res. 2013, 18(1). "
• Domenico, F. Di.; Foppoli, C.; Coccia, R.; Perluigi, M. Antioxidants in Cervical Cancer:
Chemopreventive and Chemotherapeutic Effects of Polyphenols. Biochim. Biophys. Acta -
Mol. Basis Dis. 2012, 1822, 737–747."
• Goncalves, T. L.; Erthal, F.; Corte, C. L. D.; Mller, L. G.; Piovezan, C. M.; Nogueira, C. W.;
Rocha, J. B. T. Involvement of oxidative stress in the pre-malignant and malignant states of
cervical cancer in women. Clin. Biochem. 2005, 38(12), 1071-1075. "
• Subramanyam, D.; Subbaiah, K.; Rajendra, W.; Lokanatha, V. Serum Selenium
Concentration and Antioxidant Activity in Cervical Cancer Patients before and after
Treatment. Exp Oncol. 2013, 35, 97–100."
• Cavallo, F.; De Giovanni, C.; Nanni, P.; Forni, G.; Lollini, P. L. The Immune Hallmarks of
Cancer. Cancer Immunology, Immunotherapy. 2011, 60, 319–326."
• Hanahan, D.; Weinberg, R. A. Hallmarks of Cancer: The next Generation. Cell. 2011,144,
646–674."
• Moon, H. J.; Park, W. H. Butylated Hydroxyanisole Inhibits the Growth of HeLa Cervical
Cancer Cells via Caspase-Dependent Apoptosis and GSH Depletion. Mol. Cell. Biochem.
2011, 349, 179–186."
• Jiang, B.; Xiao, S.; Khan, M. A.; Xue, M. Defective Antioxidant Systems in Cervical Cancer.
Tumor Biol. 2013, 34, 2003–2009."
• Kolanjiappan, K.; Manoharan, S.; Kayalvizhi, M. Measurement of Erythrocyte Lipids, Lipid
Peroxidation, Antioxidants and Osmotic Fragility in Cervical Cancer Patients. Clin. Chim.
Acta 2002, 326, 143–149."
• Tong, S.-Y.; Lee, J.-M.; Song, E.-S.; Lee, K.-B.; Kim, M.-K.; Lee, J.-K.; Son, S.-K.; Lee, J.-
P.; Kim, J.-H.; Kwon, Y.-I. Functional Polymorphism in Manganese Superoxide Dismutase
and Antioxidant Status: Their Interactions on the Risk of Cervical Intraepithelial Neoplasia
and Cervical Cancer. Gynecol. Oncol. 2009, 115, 272–276."
• Young, I. S.; Woodside, J. V. Antioxidants in Health and Disease. J. Clin. Pathol. 2001, 54,
176-186. "
• Bosch, F. X.; Lorincz, A.; Munoz, N.; Meijer, C. J. L. M.; Shah, K. V. The Causal Relation
between human papillomavirus and cervical cancer. J Clin Pathol. 2002, 55, 244-265. "
I would like to thank Dr. Dawe for her hard work
and dedication towards her students. A special
thank you to the library staff for their
contributions, and to my peers for their editing
and input. This poster would not be made
without the help of FOSSA for printing my
poster. I would not have be able to complete this
poster without the guidance and assistance of
these special people. "
Deanna Molson
Department of Chemistry, Wilfrid Laurier University"
The Effects of Antioxidants on the Prevention
and Treatment of Cervical Cancer
• Curcumin, EGCG, and resveratrol prove to have molecular
mechanisms that can sustain chemopreventive and
chemotherapeutic treatments"
• Polyphenols have chemosensitizing and radiosensitizing abilities
within cervical cancer models"
• Curcumin treatment suggests its significance in the
chemoprevention of cervical lesions "
• EGCG treatments determined a 69% response rate in the
prevention of HPV-related cervical lesions after green tea extraction
therapy"
• Studies of resveratrol show that this compound demonstrated a
growth-inhibitory anticancer effect on uterine cancer cells,
supporting possible treatment of cervical carcinogenesis"
• A study conducted by Zhu et al., on the effects of polyphenol
extracts from Phyllanthus emblica (PEEP), showed that PEEP was
effective in inhibiting HeLa (cervical cancer) cell proliferation and
inducing apoptosis
Graph 1. Polyphenol extract of Phyllanthus emblica(PEEP) inhibits HeLa
cell proliferation. !
Zhu, X.; Wang, J.; Ou, Y.; Han, W.; Li, H. Polyphenols extract of Phyllanthus emblica (PEEP)
induces inhibition of cell proliferation and triggers apoptosis in cervical cancer cells. Eur J Med
Res. 2013, 18(1). "
• The positive correlation between vitamin C depletion and lipid
peroxidation formation indicates that dietary supplementation with
vitamin C is now considered as an adjuvant in cancer therapy"
• Avoiding antioxidant deficiency through supplementation and
natural intake of berries, nuts, turmeric, green tea and grapes can
aid in the prevention of cervical cancer development "
• Antioxidants such as beta-carotene are good forms of treatment
as well as preventive aids because they act as immune boosters
to fight cancer cells and can convert to vitamin A within the body,
which is a proven anti-cancer agent"
• Another source of treatment can be gained through vaccines, a
form of immunotherapy, which have been proven to be more
effective than traditional cancer treatments, such as
chemotherapy"
• The discovery of a successful form of
treatment and prevention for cervical cancer is
significantly important due to its high
prevalence in women worldwide"
• The natural properties of antioxidants, such as
their ability to inhibit cell growth and reduce
oxidative stress, make them exceptional
candidates in the prevention of cervical
carcinogenesis"
• Consumption of high antioxidant containing
foods is recommended during treatment"
• Studies have determined that low antioxidant
levels and high oxidative stress levels are
associated with cervical cancer patients"
• There is a positive correlation between
antioxidant usage and the inhibition of cell
growth in patients with cervical cancer"
• Future research should focus upon increasing
preventative care associated to antioxidant
therapies"
Domenico, F. Di.; Foppoli, C.; Coccia, R.; Perluigi, M. Antioxidants in Cervical Cancer: Chemopreventive and
Chemotherapeutic Effects of Polyphenols. Biochim. Biophys. Acta - Mol. Basis Dis. 2012, 1822, 737–747. "
Figure 2. Polyphenol Compounds: Properties and Sources !
Introduction!
Oxidative Stress!
Polyphenols!
Clinical Trial Results! Conclusion!
References!
Acknowledgments!
Prevention and Treatment!
Figure 1.!
Effect of
antioxidant
deficiency on
cervical cancer
development. Dietary
deficiency of antioxidants
or a genetic defect in
antioxidant enzymes
creates oxidative stress,
which may lead to DNA
damage in cervical cells.
This damage makes cells
vulnerable to HPV
infection which is a major
factor in cervical cancer
development. !
Jiang, B.; Xiao, S.; Khan, M. A.; Xue, M. Defective Antioxidant Systems in Cervical Cancer. Tumor
Biol. 2013, 34, 2003–2009."