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

• DOI: 10.1007/s10495-006-4003-z
• Publication Date: 2006-03-06T12:45:17Z
• Authors: C. J. Lee; J. S. Han; C. Y. Seo; T. H. Park; H. C. Kwon; J. S. Jeong; I. H. Kim; J. Yun; Y. S. Bae; J. Y. Kwak; J. I. Park
• Keywords: Pioglitazone; XIAP; Thiazolidinedione

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.