Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway

Tony Tong Lin Wu, Ho Shan Niu, Li Jen Chen, Juei Tang Cheng, Yat Ching Tong

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalEuropean Journal of Pharmacology
Volume775
DOIs
Publication statusPublished - 2016 Mar 15

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PPAR delta
Prostatic Neoplasms
Apoptosis
Cell Survival
Small Interfering RNA
Flow Cytometry
Up-Regulation
Western Blotting
telmisartan
Peroxisome Proliferator-Activated Receptors
G1 Phase
RNA Interference
Cell Cycle Checkpoints
Cultured Cells

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Wu, Tony Tong Lin ; Niu, Ho Shan ; Chen, Li Jen ; Cheng, Juei Tang ; Tong, Yat Ching. / Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway. In: European Journal of Pharmacology. 2016 ; Vol. 775. pp. 35-42.
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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.",
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Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway. / Wu, Tony Tong Lin; Niu, Ho Shan; Chen, Li Jen; Cheng, Juei Tang; Tong, Yat Ching.

In: European Journal of Pharmacology, Vol. 775, 15.03.2016, p. 35-42.

Research output: Contribution to journalArticle

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