Molecular mechanism of hepatocellular carcinoma-specific antitumor activity of the novel thienopyridine derivative TP58

  • Authors:
    • Rui Zhou
    • Wen-Jun Huang
    • Zhi-Yun Guo
    • Lei Li
    • Xiao-Rong Zeng
    • Ya-Qi Deng
    • Feng-Yun Hu
    • Ai-Ping Tong
    • Li Yang
    • Jin-Liang Yang
  • View Affiliations

  • Published online on: April 23, 2012     https://doi.org/10.3892/or.2012.1776
  • Pages: 225-231
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Abstract

Despite progress made in the treatment of hepatocellular carcinoma (HCC), there is no curable treatment. Novel therapies are therefore needed. In our previous study on the design and synthesis of a small molecular inhibitor targeting Aurora kinase, we discovered a novel thienopyridine derivative compound (1g, TP58) which displayed the most potent and relatively specific inhibition of the proliferation of HepG2 human hepatoma cells in vitro. However, the molecular mechanism remains to be elucidated. Herein, in vitro and in vivo studies were conducted to further verify its antitumor activity against HCC. cDNA microarray and two-dimensional protein gel electrophoresis technology were utilized to elucidate the mechanism of HCC-specific inhibition of TP58. Flow cytometry analysis displayed that TP58 can significantly induce G0/G1 arrest in HepG2 cells. Sixteen genes involved in cell cycle regulation were found to be dysregulated following TP58 treatment using microarray technology. Nine proteins whose expression was altered (corresponding to 10 spots identified as differentially expressed) were identified by proteomic analysis. Further study showed that TP58 can modulate the expression of some liver-enriched transcription factors (LETFs) and liver-specific marker genes, such as hepatic nuclear factor (HNF-4) and α-fetoprotein (AFP). These findings may help explain the mechanism of HCC-specific antitumor activity of TP58 and provide some useful insight for anti-HCC drug design and future use of thienopyridine derivatives in HCC therapy.

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July 2012
Volume 28 Issue 1

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

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Spandidos Publications style
Zhou R, Huang W, Guo Z, Li L, Zeng X, Deng Y, Hu F, Tong A, Yang L, Yang J, Yang J, et al: Molecular mechanism of hepatocellular carcinoma-specific antitumor activity of the novel thienopyridine derivative TP58. Oncol Rep 28: 225-231, 2012
APA
Zhou, R., Huang, W., Guo, Z., Li, L., Zeng, X., Deng, Y. ... Yang, J. (2012). Molecular mechanism of hepatocellular carcinoma-specific antitumor activity of the novel thienopyridine derivative TP58. Oncology Reports, 28, 225-231. https://doi.org/10.3892/or.2012.1776
MLA
Zhou, R., Huang, W., Guo, Z., Li, L., Zeng, X., Deng, Y., Hu, F., Tong, A., Yang, L., Yang, J."Molecular mechanism of hepatocellular carcinoma-specific antitumor activity of the novel thienopyridine derivative TP58". Oncology Reports 28.1 (2012): 225-231.
Chicago
Zhou, R., Huang, W., Guo, Z., Li, L., Zeng, X., Deng, Y., Hu, F., Tong, A., Yang, L., Yang, J."Molecular mechanism of hepatocellular carcinoma-specific antitumor activity of the novel thienopyridine derivative TP58". Oncology Reports 28, no. 1 (2012): 225-231. https://doi.org/10.3892/or.2012.1776