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Volume 3
August 5-6, 2019 | Singapore
CANCER RESEARCH AND PHARMACOLOGY
STRUCTURAL BIOCHEMISTRY, STEM CELLS AND MOLECULAR BIOLOGY
24
th
International Conference on
International Congress on
&
Cancer Research 2019 & Structural Biochemistry 2019
August 5-6, 2019
Journal of Cancer and Metastasis Research
Clin Psychol Cog Sci, Volume 3
Oncofertility: Effect of chemotherapeutics and gamma tocopherol (gT) on breast cancer
and primary-derived ovarian cells
Fiona Young
Flinders University, Australia
Statement of the Problem
: Premenopausal breast-
cancer patients are treated with a combination
of chemotherapeutics, commonly doxorubicin
(adriamycin) and cyclophosphamide (‘AC’), but
the combined toxicity of ‘AC’
in vitro
has not been
reported. Additionally, ‘AC’-treated breast cancer
survivors suffer premature ovarian failure and adverse
effects caused by estrogen (E2) depletion. Each
chemotherapeutic generates reactive oxygen species
(ROS). Gamma- tocopherol (gT), a constituent of
antioxidant Vitamin E, has anticancer activity. The
aims were to examine the hypotheses that exposing
a human breast cancer cell-line (MCF7) to AC+gT
would reduce ROS, but gT would maintain anti-
cancer activity. Secondly, that AC+gT would be less
cytotoxic to primary-derived ovarian cells than ‘AC’.
Methodology & Findings
: MCF7 cells were exposed to doxorubicin (Dox), 4-hydroxyperoxy-cyclophosphamide (CYC),
Dox+CYC, gT, and Dox+CYC+gT
in vitro
. Doxorubicin, and gT, but not CYC, caused dose- dependent cytotoxicity. Dox+CYC
caused significant cytotoxicity similar to doxorubicin alone. Dox+CYC+gT caused significantly more MCF7-cell death than
Dox+CYC.
Follicles (an egg surrounded by proliferating cells) from mouse ovaries were cultured in Matrigel. Follicle diameters and E2
synthesis increased under control conditions. The percentages of viable cells per follicle after 6d in 0.3% DMSO solvent control
(for gT) were 60±9%, and 57±14% after exposure to the MCF7-derived EC25 value for gT. Exposure to the MCF7-derived EC25
values for Dox+CYC resulted in 16±5% (p<0.05, 37% of control), whereas Dox+CYC+gT (MCF7:EC25+EC25+EC25) resulted
in 44±7% viable cells per follicle (74% of control).
Conclusion & Significance
: Hypotheses were supported: gT increased Dox+CYC cytotoxicity against MCF7 cancer cells but
decreased Dox+CYC cytotoxicity towards primary-derived proliferating ovarian cells. gT anti-cancer mechanism of action
requires elucidation, but antioxidant activity may protect follicles against chemotherapeutic cytotoxicity.
Fiona.Young@Flinders.edu.au