Di-(2-ethylhexyl) phthalate suppresses tamoxifen-induced apoptosis in GH3 pituitary cells.
Tamoxifen, an estrogen receptor antagonist, has been clinically used as an antitumor drug and induces apoptosis in GH3 pituitary cells. Although di-(2-ethylhexyl) phthalate (DEHP) is a well-known environmental estrogen and the exposure to this chemical is well expected, reports are limited regarding effects of DEHP on tamoxifen-induced apoptosis in pituitary cells. In the cytotoxicity assay, the reduced cell viability in tamoxifen-treated GH3 cells was reversed by DEHP (250 microM) treatment for 4 days. To characterize cell death, cells were stained using Hoechst 33258. Apoptotic morphological change such as chromatin condensation induced by tamoxifen was suppressed by treatment with DEHP. Flow cytometric analysis revealed that the number of apoptotic cells induced by tamoxifen was significantly decreased by DEHP treatment. Enhanced poly (ADP-ribose) polymerase (PARP) cleavage by tamoxifen treatment was also inhibited by DEHP. These results suggest that DEHP suppresses tamoxifen-induced apoptosis in association with its estrogenic effect in GH3 cells and might counteract the therapeutic effect of tamoxifen.
Kim
H-S
HS
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Sapporo 060-0818, Japan.
Ishizaka
M
M
Kazusaka
A
A
Fujita
S
S
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000737:chemistry; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005434:Flow Cytometry; D008856:Microscopy, Fluorescence; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology; D010968:Plasticizers / Q000633:toxicity; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013629:Tamoxifen / Q000633:toxicity*
D018931:Antineoplastic Agents, Hormonal; D010968:Plasticizers; D013629:Tamoxifen; D004051:Diethylhexyl Phthalate; D011065:Poly(ADP-ribose) Polymerases; D006690:Bisbenzimidazole