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Article

The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells

  • Authors:
    • Kai-Sheng Liu
    • Yi Zhang
    • Wei-Chao Ding
    • Shao-Xiang Wang
    • Yang-Fei Xiang
    • Pan Yang
    • Zhen-Ping Chen
    • Kai Zheng
    • Zhong Liu
    • Min Xia
    • Yi-Fei Wang
  • View Affiliations / Copyright

    Affiliations: Institute of Biomedicine, Jinan University, Guangzhou 510632, P.R. China
  • Pages: 2276-2284
    |
    Published online on: October 17, 2012
       https://doi.org/10.3892/ijo.2012.1670
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Abstract

BJ-B11 is a selective heat shock protein 90 (Hsp90) inhibitor that has been reported to possess significant antitumor activity in multiple types of cancer cells; however, the mechanism of action needs to be further clarified. We investigated, for the first time, the antitumor activity and the molecular mechanism underlying growth inhibition in Eca-109 cells. The results revealed that BJ-B11 inhibited the proliferation of Eca-109 cells in a time- and concentration-dependent manner, with 50% inhibitory concentration (IC50) values of 0.31±0.01 µM after 48-h incubation. BJ-B11 induced concentration-dependent G2/M cell cycle arrest and apoptosis. The cleavage of caspase 3 and PARP signals detected might originate from mitochondrial dysfunction, which was supported by the results of reactive oxygen species (ROS) production, cytochrome c release and the mitochondrial membrane potential (MMP) reduction. The general caspase inhibitor Z-VAD-fmk did not completely abolish BJ-B11-induced cell death. Furthermore, inhibition of the Akt/mTOR/p70S6K signaling pathway might be involved in the process of BJ-B11-induced autophagy, which was characterized by the production of autophagic vacuoles and upregulation of LC3-II protein in a time- and concentration-dependent manner. Meanwhile, the general autophagy inhibitor 3-MA decreased the apoptotic ratio. Furthermore, BJ-B11 induced the polymerization of cytoskeleton β-tubulin and F-actin. Taken together, our results suggest that the growth inhibition of Eca-109 cells induced by BJ-B11 may result from the induction of G2/M cell cycle arrest, apoptosis and autophagy.
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Copy and paste a formatted citation
Spandidos Publications style
Liu K, Zhang Y, Ding W, Wang S, Xiang Y, Yang P, Chen Z, Zheng K, Liu Z, Xia M, Xia M, et al: The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells. Int J Oncol 41: 2276-2284, 2012.
APA
Liu, K., Zhang, Y., Ding, W., Wang, S., Xiang, Y., Yang, P. ... Wang, Y. (2012). The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells. International Journal of Oncology, 41, 2276-2284. https://doi.org/10.3892/ijo.2012.1670
MLA
Liu, K., Zhang, Y., Ding, W., Wang, S., Xiang, Y., Yang, P., Chen, Z., Zheng, K., Liu, Z., Xia, M., Wang, Y."The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells". International Journal of Oncology 41.6 (2012): 2276-2284.
Chicago
Liu, K., Zhang, Y., Ding, W., Wang, S., Xiang, Y., Yang, P., Chen, Z., Zheng, K., Liu, Z., Xia, M., Wang, Y."The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells". International Journal of Oncology 41, no. 6 (2012): 2276-2284. https://doi.org/10.3892/ijo.2012.1670
Copy and paste a formatted citation
x
Spandidos Publications style
Liu K, Zhang Y, Ding W, Wang S, Xiang Y, Yang P, Chen Z, Zheng K, Liu Z, Xia M, Xia M, et al: The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells. Int J Oncol 41: 2276-2284, 2012.
APA
Liu, K., Zhang, Y., Ding, W., Wang, S., Xiang, Y., Yang, P. ... Wang, Y. (2012). The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells. International Journal of Oncology, 41, 2276-2284. https://doi.org/10.3892/ijo.2012.1670
MLA
Liu, K., Zhang, Y., Ding, W., Wang, S., Xiang, Y., Yang, P., Chen, Z., Zheng, K., Liu, Z., Xia, M., Wang, Y."The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells". International Journal of Oncology 41.6 (2012): 2276-2284.
Chicago
Liu, K., Zhang, Y., Ding, W., Wang, S., Xiang, Y., Yang, P., Chen, Z., Zheng, K., Liu, Z., Xia, M., Wang, Y."The selective Hsp90 inhibitor BJ-B11 exhibits potent antitumor activity via induction of cell cycle arrest, apoptosis and autophagy in Eca-109 human esophageal squamous carcinoma cells". International Journal of Oncology 41, no. 6 (2012): 2276-2284. https://doi.org/10.3892/ijo.2012.1670
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