ATP depletion as a consequence of hypoxia enhances tamoxifen antiproliferative effects in T47D breast carcinoma cells.
Tamoxifen causes a mitochondrial transmembrane potential dysfunction and ATP depletion, which may play a role in tamoxifen cytotoxicity. Administration of oligomycin-2 deoxy glucose (2DG) enhanced tamoxifen antiproliferative effects, which may be due to exacerbated ATP depletion following tamoxifen and oligomycin-2DG coadministration. Sodium nitroprusside (SNP) did not significantly change tamoxifen responsiveness at 0.1, 0.5, and 1 mM; however, 2 mM SNP hampered tamoxifen effects on cell proliferation and cell cycle. Oligomycin-2DG neither changed iNOS expression nor altered its attenuated expression due to tamoxifen exposure, suggesting that ATP depletion-mediated sensitivity to tamoxifen seems to be apart from iNOS.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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M
Seyedabadi
M H
MH
Ghahremani
S N
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Ostad
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000963:Antimetabolites / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003847:Deoxyglucose / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D000255:Adenosine Triphosphate; D003847:Deoxyglucose