Pioglitazone, a synthetic ligand for PPARgamma, induces apoptosis in RB-deficient human colorectal cancer cells

Apoptosis : an International Journal on Programmed Cell Death
C J LeeJ I Park

Abstract

No published data are available about the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the role of PPARgamma in retinoblastoma protein (RB)-deficient human colorectal cancer (CRC) cells (SNU-C4 and SNU-C2A). Our aim was to investigate whether PPARgamma is expressed in SNU-C4 and SNU-C2A cells and to elucidate possible molecular mechanisms underlying the effect of pioglitazone, a synthetic ligand for PPARgamma, on cell growth in these cell lines. RT-PCR and Western blot analysis showed that both human CRC cell lines expressed PPARgamma mRNA and protein. Pioglitazone inhibited the cell growth of both cell lines through G2/M phase block and apoptosis. In addition, pioglitazone caused a down-regulation of the X chromosome-linked inhibitor of apoptosis (XIAP), Bcl-2, and cyclooxygenase-2 (COX-2) under conditions leading to PPARgamma down-regulation. These results suggest that pioglitazone may have therapeutic relevance or significance in the treatment of human CRC, and the down-regulation of XIAP, Bcl-2, and COX-2 may contribute to pioglitazone-induced apoptosis in these and other RB-deficient cell lines and tumors.

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Citations

Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Gregory T Robbins, Daotai Nie
Oct 2, 2012·PPAR Research·Joo-In Park, Jong-Young Kwak
Apr 25, 2009·PPAR Research·Ashlee B CarterJosep Bassaganya-Riera
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Nov 8, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Seong-Hoon YunJong-Young Kwak
May 15, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qiang WangQingyun Zeng
Sep 10, 2020·Life Sciences·Kaili LiuPeizhi Ma
Aug 11, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bo Liu, Shuo Yu
Feb 18, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yongji LiuFang Ju
Apr 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mei HanZhi-Wu Han

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