Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma

Tatsuo Okui, Tsuyoshi Shimo, Nur Mohammad Monsur Hassan, Takuya Fukazawa, Naito Kurio, Munenori Takaoka, Yoshio Naomoto, Akira Sasaki

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Heat-shock protein 90 (HSP90) is a major cellular chaperone protein. HSP90 supports the correct conformation, stabilization, activation, and localization of 'client' oncoproteins, many of which are involved in tumor progression. Therefore, the use of HSP90 inhibitors has become a new strategy in antitumor therapy. However, the effects of an HSP90 inhibitor on oral squamous cell carcinoma are still unclear. NVP-AUY922 (Novartis) is a novel 4,5-diaryloxazole adenosine triphosphate-binding site HSP90 inhibitor. In this study, we investigated the antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. NVP-AUY922 inhibited the proliferation of oral squamous cell carcinoma cells in vitro. NVP-AUY922 caused degradation of client protein inducing ErbB2, p-Akt, p-S6, hypoxia-inducible factor 1-α (HIF1-α) and vascular endothelial growth factor (VEGF) and up-regulation of HSP70 in HSC-2 oral squamous cell carcinoma. NVP-AUY922 increased the expression of cleaved caspase-3 and induced apoptosis in HSC-2 cells. Treatment of NVP-AUY922 induced a robust antitumor response and suppressed p-Akt and VEGF expression in an HSC-2 xenograft model. In summary, NVP-AUY922 exhibits in vitro and in vivo efficiency against oral squamous cell carcinoma, representing a promising therapeutic approach for oral squamous cell carcinoma.

Original languageEnglish
Pages (from-to)1197-1204
Number of pages8
JournalAnticancer research
Volume31
Issue number4
Publication statusPublished - Apr 1 2011

Keywords

  • HSP90 inhibitor
  • NVP-AUY922
  • Oral squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Okui, T., Shimo, T., Hassan, N. M. M., Fukazawa, T., Kurio, N., Takaoka, M., Naomoto, Y., & Sasaki, A. (2011). Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. Anticancer research, 31(4), 1197-1204.