Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells.

  • Authors:
    • Y H Choi
    • J H Baek
    • M A Yoo
    • H Y Chung
    • N D Kim
    • K W Kim
  • View Affiliations

  • Published online on: September 1, 2000     https://doi.org/10.3892/ijo.17.3.565
  • Pages: 565-636
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Abstract

Previous results indicate that ursolic acid (UA), a pentacyclic triterpene acid, has strong cytotoxic activity and effectively induces growth arrest in a variety of systems. However, the molecular mechanisms underlying anti-tumorigenic or chemopreventive activities of UA are poorly understood. To further determine the mechanism of UA, we investigated the effects of UA on the growth of human prostate epithelial cells. Upon treatment with UA, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin and DNA fragmentation. These apoptotic effects of UA were accompanied by proteolytic cleavage of specific target proteins such as PARP, beta-catenin and Rad51 proteins suggesting the possible involvement of caspases. Western blotting and in vitro assay demonstrated that processing/activation of at least four caspases (caspase-1, -3, -8 and -9) accompanies the generation of UA-mediating apoptotic cell death. In addition to activation of caspases, the down-regulation of c-IAPs family proteins, which suppress the apoptotic death signaling by the direct inhibition of activated caspases, was also observed. However, UA did not affect both the level of p53 expression and the alteration of the balance between Bcl-2 and Bax expression. These data suggest that apoptotic signals evoked by UA treatment may converge caspases activation through down-regulation of c-IAPs family and without mitochondrial dysfunction.

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Sep 2000
Volume 17 Issue 3

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

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Spandidos Publications style
Choi Y, Baek J, Yoo M, Chung H, Kim N and Kim K: Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells.. Int J Oncol 17: 565-636, 2000
APA
Choi, Y., Baek, J., Yoo, M., Chung, H., Kim, N., & Kim, K. (2000). Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells.. International Journal of Oncology, 17, 565-636. https://doi.org/10.3892/ijo.17.3.565
MLA
Choi, Y., Baek, J., Yoo, M., Chung, H., Kim, N., Kim, K."Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells.". International Journal of Oncology 17.3 (2000): 565-636.
Chicago
Choi, Y., Baek, J., Yoo, M., Chung, H., Kim, N., Kim, K."Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells.". International Journal of Oncology 17, no. 3 (2000): 565-636. https://doi.org/10.3892/ijo.17.3.565