Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27640
Title
Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells
File
Description

Abstract

Heat shock protein 90 (Hsp90) is constitutively expressed at 2‑10‑fold higher levels in tumor cells compared to normal cells, suggesting that it may be critically important for tumor cell growth and survival. These features make Hsp90 a potential target for anticancer drug development. Inhibition of Hsp90 activity not only results in rapid degradation of Hsp90 client proteins but also induces apoptosis of various tumor cells. Hsp90 also plays an important role in autophagy. An Hsp90 inhibitor induces autophagy through inhibition of mTOR. It is still under debate whether chemotherapy‑induced autophagy in tumor cells is a protective response or is invoked to promote cell death. The aim of this study was to examine the effects of the Hsp90 inhibitor, geldanamycin (GA), on KTHOS osteosarcoma cells. We further examined whether a combination of GA and the autophagy inhibitor 3‑methyladenine (3‑MA) enhanced GA‑induced apoptosis in KTHOS cells. GA had an inhibitory effect on cell proliferation and inhibited the Akt/mTOR signaling pathway in KTHOS cells. GA alone induced autophagy and apoptosis in KTHOS cells, but treatment with a combination of GA and 3‑MA suppressed autophagy and induced apoptosis to a much greater extent than GA alone in these cells. It was considered that the autophagy inhibitor 3‑MA suppressed a protective mechanism induced by Hsp90 inhibitor in tumor cells and induced apoptosis. Therefore, the combination of an Hsp90 inhibitor and an autophagy inhibitor may be an effective treatment for osteosarcoma because this combination effectively induces apoptotic pathways.

(医博甲601)

Author
著者 森 正樹
著者(ヨミ) モリ マサキ
著者(別表記) Mori Masaki
Publication Title
International Journal of Oncology
Publication Title Alternative
Int J Oncol.
Volume
46
Issue
1
Start Page
47
End Page
54
Publisher
Spandidos Publications
Published Date
2014-10-23
ISSN
1019-6439
NCID
AA10992511
PMID
25351442
DOI
10.3892/ijo.2014.2727
Resource Type
Thesis or Dissertation
Language
eng
Relation
PMCID: PMC4238730
Resource URL
https://doi.org/10.3892/ijo.2014.2727
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238730/
Rights
Copyright:© Mori et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 3.0](https://creativecommons.org/licenses/by/3.0/).
"This is the Publisher's Version of the following article: Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells; International Journal of Oncology; Volume 46 Issue 1 (2014) Pages: 47-54; doi: 10.3892/ijo.2014.2727, which has been published in final form at https://doi.org/10.3892/ijo.2014.2727 . "
Text Version
ETD
Grant ID
博甲第601号
Grant Date
2015-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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