The effect of peroxisome proliferator-activated receptor-gamma ligand on urological cancer cells.
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.
Yoshimura
Rikio
R
Department of Urology, Osaka City University Graduate School of Medicine, University Hospital, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan. jasmin@med.osaka-cu.ac.jp
Matsuyama
Masahide
M
Hase
Taro
T
Tsuchida
Kenji
K
Kuratsukuri
Katsuyuki
K
Kawahito
Yutaka
Y
Sano
Hajime
H
Segawa
Yoshihiro
Y
Nakatani
Tatsuya
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D002839:Chromans / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008024:Ligands; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077288:Troglitazone; D014571:Urologic Neoplasms / Q000188:drug therapy*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000970:Antineoplastic Agents; D002839:Chromans; D007155:Immunologic Factors; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone; D015230:Prostaglandin D2