Apoptosis in cervical cancer cells: implications for adjunct anti-estrogen therapy for cervical cancer.
BACKGROUND
Many tumors show dependence on estrogen for growth and establishment of drug resistance. We examined the effects of estrogen on cervical cancer cells exposed to apoptotic agents including drugs used for treatment.


METHODS
We tested the effect of estradiol on apoptosis in three cervical cancer cell lines. Apoptosis was measured by endonucleolytic degradation of DNA. Bcl-2 was measured by Western analysis.


RESULTS
Estradiol reduced the percentage of cells undergoing apoptosis after exposure to the DNA-damaging agents UVB, mitomycin-C and cisplatin. Protection against taxol-induced apoptosis was marginal. Protection was independent of HPV gene expression, and not specific to apoptosis induced by DNA damage, since estradiol significantly reduced the number of apoptotic cells produced after exposure to indole-3-carbinol (I3C), a non-genotoxic phytochemical effective in preventing HPV-induced tumors. Higher concentrations of I3C overcame the anti-apoptotic effect of estradiol. Treatment with I3C resulted in loss of the survival protein Bcl-2, and estradiol partially reversed this effect.


CONCLUSIONS
Estrogen protects cervical cancer cells treated with DNA-damaging agents; UVB, mitomycin-C and cisplatin, from apoptotic death. For I3C, which induces apoptosis and is anti-estrogenic, the amount of apoptosis versus survival and the level of Bcl-2 depend on the I3C/estradiol ratio.
Chen
Dazhi
D
North Shore-Long Island Jewish Research Institute, 350 Community Drive, Manhasset, NY 11030, USA.
Carter
Timothy H
TH
Auborn
Karen J
KJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000009:adverse effects / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D014466:Ultraviolet Rays; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D007211:Indoles; D004958:Estradiol; D016685:Mitomycin; C016517:indole-3-carbinol; D017239:Paclitaxel; D002945:Cisplatin