The effect of peroxisome proliferator-activated receptor-gamma ligand on urological cancer cells.

Abstract

Peroxisome proliferator activator-receptor (PPAR)-gamma ligand induces growth arrest of cancer cells through apoptosis. In this study, we examined the effects of PPAR-gamma inhibitors on cell proliferation in renal cell carcinoma (RCC), bladder tumor (BT), and prostatic carcinoma (PC) cell lines. We investigated the inhibitory effect of PPAR-gamma ligands, troglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) on RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. PPAR-gamma ligands (troglitazone and 15dPGJ2) induced the reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT, and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, clearly showed marked inhibition of cell proliferation using troglitazone and 15dPGJ2. All PPAR-gamma inhibitors stopped the growth of all RCC, BT and PC cells. Cells treated with PPAR-gamma inhibitors showed chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies), and cytoplasmic condensation. These cellular changes were typically redundant characteristics of apoptosis. PPAR-gamma ligands may mediate potent antiproliferative effects against RCC, BT and PC cells through differentiation. Thus, PPAR-gamma may become a new target in treatment of urological tumors.

• Authors: Rikio Yoshimura, Masahide Matsuyama, Taro Hase, Kenji Tsuchida, Katsuyuki Kuratsukuri, Yutaka Kawahito, Hajime Sano, Yoshihiro Segawa, Tatsuya Nakatani
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 12 Issue 6 Pg. 861-5 (Dec 2003) ISSN: 1107-3756 [Print] Greece
• PMID: 14612958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxy-delta(12,14)-prostaglandin J2
• Antineoplastic Agents
• Chromans
• Immunologic Factors
• Ligands
• Receptors, Cytoplasmic and Nuclear
• Thiazolidinediones
• Transcription Factors
• Troglitazone
• Prostaglandin D2

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Division (physiology)
• Chromans (pharmacology)
• Humans
• Immunologic Factors (pharmacology)
• Ligands
• Prostaglandin D2 (analogs & derivatives, pharmacology)
• Receptors, Cytoplasmic and Nuclear (antagonists & inhibitors, metabolism)
• Thiazolidinediones (pharmacology)
• Transcription Factors (antagonists & inhibitors, metabolism)
• Troglitazone
• Urologic Neoplasms (drug therapy)