Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human endometrioid ovarian cancer cells in vitro.
Epidemiological data have correlated consumption of nonsteroidal antinflammatory drugs with lowered risk for many types of cancer, and some recent studies indicate a reverse correlation with acetaminophen consumption and ovarian malignancy. In this study we examined effects of acetaminophen on plating, S-phase and colony growth of MDAH 2774 human endometrioid ovarian carcinoma, as well as sensitivity of this cell line to carboplatin in all three tests, and paclitaxel to clonogenic assay. Acetaminophen significantly enhanced S-phase in first 72 hours and enhanced cell population in 96 hours of plating monitorization, but decreased one week colony growth by approximately 80%, which was in the range of cytotoxic drugs. Interestingly with low dose carboplatin in first 72 hours acetaminophen enhanced cell proliferation more profoundly, but only thereafter decreased cell growth synergistically with carboplatin. It did not effect paclitaxel colony growth inhibiting acitivity. MDAH-2774 cell line lack p-53 and MSH-2, which are both 'gatekeeper' apoptosis inducing genes against genome damaging insult. Thus, presence of lower doses of oxidizing drugs may help the induction of proliferative signals, but only their sustained presence may overcome such signals and ultimately bring to cell demise.
Bilir
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A
Department of Histology and Embryology, Istanbul Medical School, Faculty of Science, Turkey. bilira@istanbul.edu.tr
Altinoz
M A
MA
Attar
E
E
Erkan
M
M
Aydiner
A
A
D000082:Acetaminophen / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000082:Acetaminophen; D016190:Carboplatin; D017239:Paclitaxel