title: 15-Deoxy-Δ12,14-prostaglandin J2 enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPARγ pathways.
abstract: 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-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ(2) in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ(2), but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ(2) 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-PGJ(2)-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ(2) activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ(2) exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPARγ.
authors.affiliation: Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Megumi
authors.initials: M
authors.lastname: Fujita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Koma
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Noboru
authors.initials: N
authors.lastname: Okamura
authors.forename: Tatsurou
authors.initials: T
authors.lastname: Yagami
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004357:Drug Synergism; D004789:Enzyme Activation; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000970:Antineoplastic Agents; D047495:PPAR gamma; D053148:Caspase 3; D004250:DNA Topoisomerases, Type II; D015230:Prostaglandin D2; D002166:Camptothecin