Priming effect of aspirin for tumor cells to augment cytotoxic action of cisplatin against tumor cells: implication of altered constitution of tumor microenvironment, expression of cell cycle, apoptosis, and survival regulatory molecules.
The present study was conducted to investigate if anti-inflammatory drug aspirin could alter the cytotoxic action of cisplatin on tumor cells. Using a transplantable T cell lymphoma in a murine model, we demonstrate that exposure to aspirin exerts a priming action on tumor cells, rendering them susceptible to induction of cell death by cisplatin with consequences on retardation of tumor progression. The priming action of aspirin on tumor cells was found to be dependent on an altered constitution of tumor microenvironment with respect to decline of acidosis and modulation in the expression of cell cycle and survival regulatory molecules like cyclin B1, cyclin D, bcl-2, bcl-xL, p53, and cytokines: IL-4, IL-10, IFN- γ & VEGF. The study also discusses possible mechanisms underlying augmentary action of aspirin on cisplatin-mediated tumor cells killing. This is the first report showing that pre-exposure of tumor cells to aspirin lowers the concentration of cisplatin to exert its cytotoxic action. The finding of this study will help in designing novel antitumor protocols with reduced dose of cisplatin.
School of Biotechnology, Banaras Hindu University, Varanasi 221 005, Uttar Pradesh, India.
Anjani
A
Kumar
Sukh Mahendra
SM
Singh
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001241:Aspirin / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D016213:Cyclins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents; D016213:Cyclins; D016207:Cytokines; D016753:Interleukin-10; D015847:Interleukin-4; D002945:Cisplatin; D001241:Aspirin