Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases

  • Authors:
    • Y. H. Choi
    • E.-O. Im
    • H. Suh
    • Y. Jin
    • W. H. Lee
    • Y. H. Yoo
    • K.-W. Kim
    • N. D. Kim
  • View Affiliations

  • Published online on: May 1, 2001     https://doi.org/10.3892/ijo.18.5.979
  • Pages: 979-984
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Abstract

The therapeutic efficacies of bile acids, such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA), have been widely demonstrated in various liver diseases, suggesting that they might protect hepatocytes against common mechanisms of liver damage. Although they have been shown to prevent apoptotic cell death in certain cell lines, we have previously reported that a novel derivative (HS-1030) of UDCA significantly inhibited cell growth and induced apoptosis in cancer cells. To develop more effective agents, we synthesized several derivatives, named HS-1183, HS-1199 and HS-1200, based on the structure of UDCA and CDCA, and investigated them for anti-proliferative activity in Jurkat cells, a human leukemic T cell line. Whereas UDCA and CDCA had no significant effects on the growth of Jurkat cells in the concentration range tested, both HS-1199 and HS-1200 completely inhibited the cell proliferation, and HS-1183 showed only a weak inhibitory activity. Furthermore, chromatin condensation, DNA ladder formation and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) were observed after treatment of novel bile acids, indicating the occurrence of apoptotic cell death, which was associated with down-regulation of caspase-3 and -8. The apoptotic manifestations such as PARP cleavage and DNA fragmentation were abolished in the presence of the tripeptide caspase inhibitor zVAD-fmk or the specific caspase-3 inhibitor DEVD-fmk. Our data thus demonstrate that novel bile acid derivatives-induced apoptosis of leukemic T cells is dependent on caspase activation.

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May 2001
Volume 18 Issue 5

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

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Spandidos Publications style
Choi YH, Im E, Suh H, Jin Y, Lee WH, Yoo YH, Kim K and Kim ND: Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases. Int J Oncol 18: 979-984, 2001.
APA
Choi, Y.H., Im, E., Suh, H., Jin, Y., Lee, W.H., Yoo, Y.H. ... Kim, N.D. (2001). Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases. International Journal of Oncology, 18, 979-984. https://doi.org/10.3892/ijo.18.5.979
MLA
Choi, Y. H., Im, E., Suh, H., Jin, Y., Lee, W. H., Yoo, Y. H., Kim, K., Kim, N. D."Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases". International Journal of Oncology 18.5 (2001): 979-984.
Chicago
Choi, Y. H., Im, E., Suh, H., Jin, Y., Lee, W. H., Yoo, Y. H., Kim, K., Kim, N. D."Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases". International Journal of Oncology 18, no. 5 (2001): 979-984. https://doi.org/10.3892/ijo.18.5.979