Trichostatin inhibits the growth of ACHN renal cell carcinoma cells via cell cycle arrest in association with p27, or apoptosis

  • Authors:
    • Woo Hyun Park
    • Chul Won Jung
    • Joon Oh Park
    • Kihyun Kim
    • Won Seog Kim
    • Young Hyuck Im
    • Mark H. Lee
    • Won Ki Kang
    • Keunchil Park
  • View Affiliations

  • Published online on: May 1, 2003     https://doi.org/10.3892/ijo.22.5.1129
  • Pages: 1129-1134
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Abstract

We investigated the in vitro effect of trichostatin (histone deacetylase inhibitor) on cell proliferation, cell cycle regulation and apoptosis in renal cell carcinoma cell lines. Trichostatin significantly inhibited the proliferation of all six cell lines examined in dose-dependent manner with IC50 of about 125-250 nM. Trichostatin (72-h incubation) induced a G1 phase arrest in ACHN, Caki-1, Caki-2 and Renca cell lines and a G2-M phase arrest in A498 cells. When we examined the effects of this drug on ACHN cells, trichostatin decreased the levels of CDK4, CDK6, cyclin D1 and cyclin A proteins. p27 protein was increased by trichostatin. In addition, trichostatin markedly enhanced the binding of p27 with CDK2 and CDK4. Furthermore, the activities of CDK2, CDK4- and CDK6-associated kinase were reduced and the lack of the CDK activity was paralleled by increased hypophosphorylation of Rb protein. Trichostatin also induced apoptosis in all the renal cell carcinoma cell lines. Apoptotic process of ACHN cells was associated with the changes of Bcl-2, caspase-9, caspase-3, caspase-7 proteins as well as mitochondria transmembrane potential (Δψm) loss. Taken together, these results demonstrate that trichostatin inhibits the growth of renal cell carcinoma cells via cell cycle arrest or apoptosis.

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May 2003
Volume 22 Issue 5

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

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Spandidos Publications style
Park WH, Jung CW, Park JO, Kim K, Kim WS, Im YH, Lee MH, Kang WK and Park K: Trichostatin inhibits the growth of ACHN renal cell carcinoma cells via cell cycle arrest in association with p27, or apoptosis. Int J Oncol 22: 1129-1134, 2003.
APA
Park, W.H., Jung, C.W., Park, J.O., Kim, K., Kim, W.S., Im, Y.H. ... Park, K. (2003). Trichostatin inhibits the growth of ACHN renal cell carcinoma cells via cell cycle arrest in association with p27, or apoptosis. International Journal of Oncology, 22, 1129-1134. https://doi.org/10.3892/ijo.22.5.1129
MLA
Park, W. H., Jung, C. W., Park, J. O., Kim, K., Kim, W. S., Im, Y. H., Lee, M. H., Kang, W. K., Park, K."Trichostatin inhibits the growth of ACHN renal cell carcinoma cells via cell cycle arrest in association with p27, or apoptosis". International Journal of Oncology 22.5 (2003): 1129-1134.
Chicago
Park, W. H., Jung, C. W., Park, J. O., Kim, K., Kim, W. S., Im, Y. H., Lee, M. H., Kang, W. K., Park, K."Trichostatin inhibits the growth of ACHN renal cell carcinoma cells via cell cycle arrest in association with p27, or apoptosis". International Journal of Oncology 22, no. 5 (2003): 1129-1134. https://doi.org/10.3892/ijo.22.5.1129