Ganetespib induces G2/M cell cycle arrest and apoptosis in gastric cancer cells through targeting of receptor tyrosine kinase signaling

  • Authors:
    • Harry Lee
    • Nipun Saini
    • Amanda B. Parris
    • Ming Zhao
    • Xiaohe Yang
  • View Affiliations

  • Published online on: July 13, 2017     https://doi.org/10.3892/ijo.2017.4073
0

Abstract

Heat shock protein 90 (HSP90) regulates several important cellular processes via its repertoire of ‘client proteins’. These client proteins have been found to play fundamental roles in signal transduction, cell proliferation, cell cycle progression and survival, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. Thus, HSP90 is an emerging target for cancer therapy. To this end, we evaluated ganetespib (STA-9090), a novel and potent HSP90 inhibitor, for its activity in gastric cancer cell lines. Ganetespib significantly inhibited the proliferation of AGS and N87 human gastric cancer cell lines and potently induced G2/M cell cycle arrest and apoptosis. Upregulation of cleaved poly(ADP-ribose) polymerase (c-PARP), c-caspase-3, c-caspase-8 and c-caspase-9 and suppression of gastric cancer‑associated HSP90 client proteins, including ErbB2, Erk, Akt, mTOR, GSK3 and Src, were observed in ganetespib-treated cells. These findings demonstrate that the ganetespib-induced mechanism of cell growth inhibition involves the activation of death receptor and mitochondrial pathways and the inhibition of receptor tyrosine kinase signaling pathways. Our study implicates ganetespib as a potential strategy for gastric cancer treatment, which warrants further preclinical and clinical investigation.

Related Articles

Journal Cover

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

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Lee, H., Saini, N., Parris, A.B., Zhao, M., & Yang, X. (1899). Ganetespib induces G2/M cell cycle arrest and apoptosis in gastric cancer cells through targeting of receptor tyrosine kinase signaling. International Journal of Oncology, 0, 0-0. https://doi.org/10.3892/ijo.2017.4073
MLA
Lee, H., Saini, N., Parris, A. B., Zhao, M., Yang, X."Ganetespib induces G2/M cell cycle arrest and apoptosis in gastric cancer cells through targeting of receptor tyrosine kinase signaling". International Journal of Oncology 0.0 (1899): 0-0.
Chicago
Lee, H., Saini, N., Parris, A. B., Zhao, M., Yang, X."Ganetespib induces G2/M cell cycle arrest and apoptosis in gastric cancer cells through targeting of receptor tyrosine kinase signaling". International Journal of Oncology 0, no. 0 (1899): 0-0. https://doi.org/10.3892/ijo.2017.4073