title: Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway.
abstract: The effect of telmisartan on prostate cancer DU145 cell survival and the underlying mechanism of apoptosis involving peroxisome proliferator-activated receptor (PPAR) pathway were investigated. Cultured DU145 cells were treated pharmacologically with telmisartan and GSK0660 (a PPAR-delta antagonist); or by RNA interference with siRNA of PPAR-delta. The treatment effects on cell survival were evaluated with cell viability assay, life and dead cell staining and flow cytometry. Western blot analysis for PPAR-delta protein expression was also performed. The results showed that telmisartan (0-80 µm) dose-dependently reduced DU145 cell survival. Flow cytometry demonstrated cancer cell cycle arrest with increase of sub-G1 phase. GSK0660 partially but significantly restored the telmisartan-treated cell viability. Similarly, siRNA of PPAR-delta significantly reversed the telmisartan-induced apoptosis. Western blot showed that telmisartan significantly increased DU145 cell PPAR-delta protein expression. Co-incubation with siRNA of PPAR-delta inhibited the telmisartan effect of PPAR-delta up-regulation. In conclusion, telmisartan induces prostate cancer DU145 cells apoptosis through the up-regulation of PPAR-delta protein expression. Pharmacological inhibition or genetic silencing of PPAR-delta activity can both reverse the telmisartan-induced apoptotic effect. Thus the PPAR-delta pathway might be a potential target for the treatment of prostate cancer.
authors: Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan; Department of Urology, School of Medicine, National Yang Ming University, Taipei, Taiwan.
authors: Tony Tong-Lin
authors: TT
authors: Wu
authors: Department of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan.
authors: Ho-Shan
authors: HS
authors: Niu
authors: Department of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan.
authors: Li-Jen
authors: LJ
authors: Chen
authors: Department of Medical Research, Chi-Mei Medical Center, Tainan City, Taiwan; Institute of Medical Sciences, Chang Jung Christian University, Tainan City, Taiwan.
authors: Juei-Tang
authors: JT
authors: Cheng
authors: Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. Electronic address: yctong@mail.ncku.edu.tw.
authors: Yat-Ching
authors: YC
authors: Tong
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D047494:PPAR delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013450:Sulfones / Q000494:pharmacology; D000077333:Telmisartan; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D001565:Benzoates; C529769:GSK0660; D047494:PPAR delta; D034741:RNA, Small Interfering; D013450:Sulfones; D013876:Thiophenes; D000077333:Telmisartan
keywords: Apoptosis; Peroxisome proliferator-activated receptor; Prostate cancer; Telmisartan