Synthetic bile acid derivatives inhibit cell proliferation and induce apoptosis in HT-29 human colon cancer cells

  • Authors:
    • Sang Eun Park
    • Hye Joung Choi
    • Su Bog Yee
    • Hae Young Chung
    • Hongsuk Suh
    • Yung Hyun Choi
    • Young Hyun Yoo
    • Nam Deuk Kim
  • View Affiliations

  • Published online on: July 1, 2004     https://doi.org/10.3892/ijo.25.1.231
  • Pages: 231-236
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Abstract

As previously demonstrated, the synthetic bile acid derivatives mediate anti-proliferative properties in a variety of human cancer cells. In the present study, the effects of the synthetic derivatives of ursodeoxycholic acid (UDCA), HS-1030 and HS-1183, and chenodeoxycholic acid (CDCA), HS-1199 and HS-1200, on the proliferation of HT-29 human colon cancer cells were investigated. Whereas UDCA and CDCA had no effect on the growth of cells in the concentration ranges we have tested, HS-1199 and HS-1200 completely inhibited cell proliferation, while HS-1030 and HS-1183 showed weak inhibitory activities. Simultaneous estimation of cell cycle parameters and apoptosis by flow cytometry showed that the synthetic bile acid derivatives produced the arrest of cell cycle progression at the G1 phase and ensuing increase of sub-G1 fraction, which resulted in the induction of apoptosis. The induction of apoptosis was confirmed by observation of cleavages of poly(ADP-ribose) polymerase and DNA fragmentation. Furthermore, Western blot analysis showed decreased expression levels of cyclin D1, cyclin E, cyclin A, Cdk2, Cdk4, and Cdk6 proteins. In addition, the synthetic bile acid derivatives markedly induced the level of Cdk inhibitor, p21WAF1/CIP1, in a p53-independent manner. Furthermore, the exposure of cells to the synthetic bile acid derivatives resulted in a decrease in the level of pRb and enhanced binding between pRb and E2F-1. Based on these data, these synthetic bile acid derivatives may serve as potential lead compounds in the treatment of colon cancer.

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July 2004
Volume 25 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Park SE, Choi HJ, Yee SB, Chung HY, Suh H, Choi YH, Yoo YH and Kim ND: Synthetic bile acid derivatives inhibit cell proliferation and induce apoptosis in HT-29 human colon cancer cells. Int J Oncol 25: 231-236, 2004
APA
Park, S.E., Choi, H.J., Yee, S.B., Chung, H.Y., Suh, H., Choi, Y.H. ... Kim, N.D. (2004). Synthetic bile acid derivatives inhibit cell proliferation and induce apoptosis in HT-29 human colon cancer cells. International Journal of Oncology, 25, 231-236. https://doi.org/10.3892/ijo.25.1.231
MLA
Park, S. E., Choi, H. J., Yee, S. B., Chung, H. Y., Suh, H., Choi, Y. H., Yoo, Y. H., Kim, N. D."Synthetic bile acid derivatives inhibit cell proliferation and induce apoptosis in HT-29 human colon cancer cells". International Journal of Oncology 25.1 (2004): 231-236.
Chicago
Park, S. E., Choi, H. J., Yee, S. B., Chung, H. Y., Suh, H., Choi, Y. H., Yoo, Y. H., Kim, N. D."Synthetic bile acid derivatives inhibit cell proliferation and induce apoptosis in HT-29 human colon cancer cells". International Journal of Oncology 25, no. 1 (2004): 231-236. https://doi.org/10.3892/ijo.25.1.231