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Trichostatin A induces bladder cancer cell death via intrinsic apoptosis at the early phase and Sp1‑survivin downregulation at the late phase of treatment

  • Authors:
    • Shou-Chieh Wang
    • Shou-Tsung Wang
    • Hung-Te Liu
    • Xiang-Yu Wang
    • She-Ching Wu
    • Lei-Chin Chen
    • Yi-Wen Liu

  • View Affiliations

  • Published online on: July 6, 2017     https://doi.org/10.3892/or.2017.5795
  • Pages: 1587-1596
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Abstract

Histone deacetylase (HDAC) inhibitors have been widely shown to result in cancer cell death. The present study investigated the mechanisms underlying the antitumor effects of the phytochemical trichostatin A (TSA), a classic pan-HDAC inhibitor, in 5,637 urinary bladder cancer cells. It was found that TSA caused cell cycle arrest at the G2/M and G1 phase accompanied by reduced expression of cyclin D1 and upregulated induction of p21. In addition, TSA induced morphological changes, reduced cell viability and apoptotic cell death in 5,637 cells through caspase-3 activation followed by PARP cleavage. The loss of mitochondrial membrane potential (MMP) indicated that TSA induced apoptosis in 5,637 cells through the intrinsic mitochondrial pathway. TSA significantly suppressed Akt activity at 12 h after treatment, suggesting that the apoptosis in the early phase was mediated by Akt inhibition. In addition, the protein level of transcription factor Sp1 was decreased at 24 h after TSA treatment, which likely led to the downregulation of survivin gene expression, and then contributed to the antitumor activity of TSA. Taken together, the present study delineated that TSA-induced growth inhibition and apoptosis in 5,637 cells was associated with pAKT inhibition and MMP loss at the early phase, followed by downregulation of Sp1 and survivin at the late phase of treatment.
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September-2017
Volume 38 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Wang S, Wang S, Liu H, Wang X, Wu S, Chen L and Liu Y: Trichostatin A induces bladder cancer cell death via intrinsic apoptosis at the early phase and Sp1‑survivin downregulation at the late phase of treatment. Oncol Rep 38: 1587-1596, 2017.
APA
Wang, S., Wang, S., Liu, H., Wang, X., Wu, S., Chen, L., & Liu, Y. (2017). Trichostatin A induces bladder cancer cell death via intrinsic apoptosis at the early phase and Sp1‑survivin downregulation at the late phase of treatment. Oncology Reports, 38, 1587-1596. https://doi.org/10.3892/or.2017.5795
MLA
Wang, S., Wang, S., Liu, H., Wang, X., Wu, S., Chen, L., Liu, Y."Trichostatin A induces bladder cancer cell death via intrinsic apoptosis at the early phase and Sp1‑survivin downregulation at the late phase of treatment". Oncology Reports 38.3 (2017): 1587-1596.
Chicago
Wang, S., Wang, S., Liu, H., Wang, X., Wu, S., Chen, L., Liu, Y."Trichostatin A induces bladder cancer cell death via intrinsic apoptosis at the early phase and Sp1‑survivin downregulation at the late phase of treatment". Oncology Reports 38, no. 3 (2017): 1587-1596. https://doi.org/10.3892/or.2017.5795