A small molecule inhibitor of ATPase activity of HSP70 induces apoptosis and has antitumor activities

Title
A small molecule inhibitor of ATPase activity of HSP70 induces apoptosis and has antitumor activities
Authors
Sung-Kyun KoJiyeon KimDeuk Chae NaSookil ParkSeong-Hyun ParkJi Young HyunKyung-Hwa BaekNam Doo Kim김낙균Young Nyun ParkSong, KiwonInjae Shin
Issue Date
2015-03
Publisher
Chemistry & biology
Citation
VOL 22, NO 3, 391-403
Abstract
The heat shock protein HSP70 plays antiapoptotic and oncogenic roles, and thus its inhibition has been recognized as a potential avenue for anticancer therapy. Here we describe the small molecule, apoptozole (Az), which inhibits the ATPase activity of HSP70 by binding to its ATPase domain and, as a result, induces an array of apoptotic phenotypes in cancer cells. Affinity chromatography provides evidence that Az binds HSP70 but not other types of heat shock proteins including HSP40, HSP60, and HSP90. We also demonstrate that Az induces cancer cell death via caspase-dependent apoptosis by disrupting the interaction of HSP70 with APAF-1. Animal studies indicate that Az treatment retards tumor growth in a xenograft mouse model without affecting mouse viability. These studies suggest that Az will aid the development of new cancer therapies and serve as a chemical probe to gain a better understanding of the diverse functions of HSP70.
URI
http://pubs.kist.re.kr/handle/201004/50638
ISSN
10745521
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KIST Publication > Article
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