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

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Abstract

No published data are available about the expression of peroxisome proliferator-activated receptor γ (PPARγ) and the role of PPARγ in retinoblastoma protein (RB)-deficient human colorectal cancer (CRC) cells (SNU-C4 and SNU-C2A). Our aim was to investigate whether PPARγ is expressed in SNU-C4 and SNU-C2A cells and to elucidate possible molecular mechanisms underlying the effect of pioglitazone, a synthetic ligand for PPARγ, on cell growth in these cell lines. RT-PCR and Western blot analysis showed that both human CRC cell lines expressed PPARγ 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 PPARγ 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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Authors and Affiliations

  1. Department of Biochemistry, Department of Biochemistry, Dong-A University College of Medicine, Busan, South Korea

    C. J. Lee, J. S. Han, C. Y. Seo, J. Yun, Y. S. Bae, J. Y. Kwak & J. I. Park

  2. Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan, South Korea

    J. S. Han, C. Y. Seo, J. Yun, Y. S. Bae, J. Y. Kwak & J. I. Park

  3. Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea

    T. H. Park & H. C. Kwon

  4. Department of Pathology, Dong-A Univesity College of Medicine, Busan, South Korea

    J. S. Jeong

  5. Division of Basic Science, National Cancer Center Research Institute, Goyang, Gyeonggi, South Korea

    I. H. Kim

  6. Department of Biochemistry, Dong-A University College of Medicine, 3 Ga 1, Dongdaesin-Dong, Seo-Gu, 602-714, South Korea

    J. I. Park

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  1. C. J. Lee
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Lee, C.J., Han, J.S., Seo, C.Y. et al. Pioglitazone, a synthetic ligand for PPARγ, induces apoptosis in RB-deficient human colorectal cancer cells. Apoptosis 11, 401–411 (2006). https://doi.org/10.1007/s10495-006-4003-z

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  • DOI: https://doi.org/10.1007/s10495-006-4003-z

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