15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPAR{gamma} pathways

Journal Article · Fri Jul 08 00:00:00 EDT 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.06.026· OSTI ID:22204997

Yamamoto, Yasuhiro ^[1]; Fujita, Megumi ^[2]; Koma, Hiromi ^[1]; Yamamori, Motohiro ^[2]; Nakamura, Tsutomu ^[1]; Okamura, Noboru ^[2]; Yagami, Tatsurou ^[1]

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1. Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan)
2. Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien-kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan)

Highlights: {yields} A topoisomerase-I inhibitor, camptothecin, exhibited synergistically toxicity with 15d-PGJ{sub 2}. {yields} The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. {yields} A PPAR{gamma} antagonist did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. {yields} The treatment of camptothecin combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. -- 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-{gamma} (PPAR{gamma}), 15-deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ{sub 2} in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ{sub 2}, but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ{sub 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 PPAR{gamma} antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ{sub 2} exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPAR{gamma}.

• OSTI ID: 22204997
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 410, Issue 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CARCINOMAS
CLINICAL TRIALS
INHIBITION
KIDNEYS
LIGANDS
PROSTAGLANDINS
RECEPTORS
TOXICITY
URACILS