Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level

  • Authors:
    • Seung Hee Yoo
    • Hye Young Kim
    • Jee Hyun Rho
    • Seon-Yong Jeong
    • Jeanho Yun
    • Il Yun
    • Hwan Tae Park
    • Young Hyun Yoo
  • View Affiliations

  • Published online on: September 7, 2015     https://doi.org/10.3892/ijo.2015.3150
  • Pages: 1783-1792
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Abstract

Previous studies reported that a Gamitrinib variant containing triphenylphosphonium (G-TPP) binds to mitochondrial Hsp90 and rapidly inhibits its activity to induce apoptosis. We investigated the mechanisms underlying the antitumor activity of G-TPP in Hep3B hepatocellular carcinoma cells. Contrary to our predictions, we observed mitochondrial elongation in the G-TPP-treated Hep3B cells undergoing apoptosis. We found that the G-TPP-induced mitochondrial elongation in Hep3B cells was caused by a decrease in the mitochondrial fission-regulating protein Drp1 rather than by changes in the mitochondrial fusion machinery proteins Mfn1 and Opa1. Furthermore, G-TPP induced G2-M phase cell cycle arrest by reducing the interaction between CDK1 and cyclin B1. Additionally, reactive oxygen species (ROS) played a pivotal role in G-TPP-induced cell death and mitochondrial elongation in Hep3B cells, and these processes are mediated by the reduced association of CDK1 with cyclin B1 and the suppressed phosphorylation of Drp1 (Ser616). Thus, G-TPP induces cell death and causes Drp1-mediated mitochondrial elongation in Hep3B cells by increasing the ROS level.
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November-2015
Volume 47 Issue 5

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

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Spandidos Publications style
Yoo SH, Kim HY, Rho JH, Jeong S, Yun J, Yun I, Park HT and Yoo YH: Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level. Int J Oncol 47: 1783-1792, 2015.
APA
Yoo, S.H., Kim, H.Y., Rho, J.H., Jeong, S., Yun, J., Yun, I. ... Yoo, Y.H. (2015). Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level. International Journal of Oncology, 47, 1783-1792. https://doi.org/10.3892/ijo.2015.3150
MLA
Yoo, S. H., Kim, H. Y., Rho, J. H., Jeong, S., Yun, J., Yun, I., Park, H. T., Yoo, Y. H."Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level". International Journal of Oncology 47.5 (2015): 1783-1792.
Chicago
Yoo, S. H., Kim, H. Y., Rho, J. H., Jeong, S., Yun, J., Yun, I., Park, H. T., Yoo, Y. H."Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level". International Journal of Oncology 47, no. 5 (2015): 1783-1792. https://doi.org/10.3892/ijo.2015.3150