Anticancer effects of the Hsp90 inhibitor 17-demethoxy-reblastatin in human breast cancer MDA-MB-231 cells.
Triple-negative breast cancer (TNBC) possesses a higher rate of distant recurrence and a poorer prognosis than other breast cancer subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client proteins are oncoproteins, and some are closely related to unfavorable factors of TNBC patients. 17-Demethoxy-reblastatin (17-DR), a novel nonbenzoquinone- type geldanamycin analog, exhibited potent Hsp90 ATPase inhibition activity. In this study, the anticancer effects of 17-DR on TNBC MDA-MB-231 cells were investigated. These results showed that 17-DR inhibited cell proliferation, induced apoptosis, and suppressed cell invasion and migration in the MDA-MB-231 cells. Down-regulation of the key Hsp90-dependent tumor-driving molecules, such as RIP1 and MMP-9, by 17-DR may be related to these effects. Taken together, our results suggest that 17-DR has potential as a therapeutic agent for the treatment of TNBC.
Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233030, P. R. China.
Qing
Q
Zhao
Cheng-Zhu
CZ
Wu
Jae Kyoung
JK
Lee
Su-Rong
SR
Zhao
Hong-Mei
HM
Li
Qiang
Q
Huo
Tao
T
Ma
Jin
J
Zhang
Young-Soo
YS
Hong
Hao
H
Liu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; C001277:geldanamycin