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

25 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 2011

Fingerprint

HSP90 Heat-Shock Proteins
Squamous Cell Carcinoma
Vascular Endothelial Growth Factor A
S 6
Hypoxia-Inducible Factor 1
Oncogene Proteins
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide
Heterografts
Caspase 3
Proteolysis
Up-Regulation
Adenosine Triphosphate
Binding Sites
Apoptosis
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. / Okui, Tatsuo; Shimo, Tsuyoshi; Hassan, Nur Mohammad Monsur; Fukazawa, Takuya; Kurio, Naito; Takaoka, Munenori; Naomoto, Yoshio; Sasaki, Akira.

In: Anticancer Research, Vol. 31, No. 4, 04.2011, p. 1197-1204.

Research output: Contribution to journalArticle

Okui, T, Shimo, T, Hassan, NMM, 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, vol. 31, no. 4, pp. 1197-1204.
Okui T, Shimo T, Hassan NMM, Fukazawa T, Kurio N, Takaoka M et al. Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. Anticancer Research. 2011 Apr;31(4):1197-1204.
Okui, Tatsuo ; Shimo, Tsuyoshi ; Hassan, Nur Mohammad Monsur ; Fukazawa, Takuya ; Kurio, Naito ; Takaoka, Munenori ; Naomoto, Yoshio ; Sasaki, Akira. / Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. In: Anticancer Research. 2011 ; Vol. 31, No. 4. pp. 1197-1204.
@article{f9d1cdb9257f4bde908a50f4bc5024ec,
title = "Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma",
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.",
keywords = "HSP90 inhibitor, NVP-AUY922, Oral squamous cell carcinoma",
author = "Tatsuo Okui and Tsuyoshi Shimo and Hassan, {Nur Mohammad Monsur} and Takuya Fukazawa and Naito Kurio and Munenori Takaoka and Yoshio Naomoto and Akira Sasaki",
year = "2011",
month = "4",
language = "English",
volume = "31",
pages = "1197--1204",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "4",

}

TY - JOUR

T1 - Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma

AU - Okui, Tatsuo

AU - Shimo, Tsuyoshi

AU - Hassan, Nur Mohammad Monsur

AU - Fukazawa, Takuya

AU - Kurio, Naito

AU - Takaoka, Munenori

AU - Naomoto, Yoshio

AU - Sasaki, Akira

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

KW - HSP90 inhibitor

KW - NVP-AUY922

KW - Oral squamous cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=79956150123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79956150123&partnerID=8YFLogxK

M3 - Article

C2 - 21508365

AN - SCOPUS:79956150123

VL - 31

SP - 1197

EP - 1204

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 4

ER -