15-Deoxy-Δ12,14-prostaglandin J2 enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPARγ pathways

Renal cell carcinoma (RCC) is chemoresistant cancer. Although several clinical trials were conducted to explore effective medications, the chemoresistance of RCC has not yet been conquered. An endogenous ligand for peroxisome proliferator-activated receptor-γ (PPARγ), 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ2 in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ2, but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ2 and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. The synergistic effect of topoisomerase-I and II inhibitors was not also detected. A PPARγ antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ2-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ2 activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ2 exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPARγ.

► A topoisomerase-I inhibitor, camptothecin, exhibited synergistically toxicity with 15d-PGJ2. ► The combination of 15d-PGJ2 and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. ► A PPARγ antagonist did not prevent Caki-2 from undergoing 15d-PGJ2-induced cytotoxicity. ► The treatment of camptothecin combined with 15d-PGJ2 activated caspase-3 more than the separate treatment.