Estrogenic activity of coumestrol, DDT, and TCDD in human cervical cancer cells.
Endogenous estrogens have dramatic and differential effects on classical endocrine organ and proliferation. Xenoestrogens are environmental estrogens that have endocrine impact, acting as both estrogen agonists and antagonists, but whose effects are not well characterized. In this investigation we sought to delineate effects of xenoestrogens. Using human cervical cancer cells (HeLa cells) as a model, the effects of representative xenoestrogens (Coumestrol-a phytoestrogen, tetrachlorodioxin (TCDD)-a herbicide and DDT-a pesticide) on proliferation, cell cycle, and apoptosis were examined. These xenoestrogens and estrogen inhibited the proliferation of Hela cells in a dose dependent manner from 20 to 120 nM suggesting, that 17-beta-estrtadiol and xenoestrogens induced cytotoxic effects. Coumestrol produced accumulation of HeLa cells in G2/M phase, and subsequently induced apoptosis. Similar effects were observed in estrogen treated cells. These changes were associated with suppressed bcl-2 protein and augmented Cyclins A and D proteins. DDT and TCDD exposure did not induce apoptosis. These preliminary data taken together, suggest that xenoestrogens have direct, compound-specific effects on HeLa cells. This study further enhances our understanding of environmental modulation of cervical cancer.
Ndebele
Kenneth
K
The Laboratory of Cancer Immunology, Target Identification and Validation, College of Science, Engineering and Technology, Jackson State University, Jackson, MS 39217, USA. kenneth.ndebele@jsums.edu
Graham
Barbara
B
Tchounwou
Paul B
PB
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003375:Coumestrol / Q000494:pharmacology*; D003634:DDT / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D004967:Estrogens; D000072317:Polychlorinated Dibenzodioxins; D019253:Proto-Oncogene Proteins c-bcl-2; D003634:DDT; D003375:Coumestrol