Hits:

Indexed by:期刊论文

Date of Publication:2014-07-01

Journal:ASIAN PACIFIC JOURNAL OF CANCER PREVENTION

Included Journals:SCIE、PubMed、Scopus

Volume:15

Issue:18

Page Number:7913-7917

ISSN No.:1513-7368

Key Words:HDAC inhibitor; drug resistance; Beclin-1; autophagy; apoptosis

Abstract:Apoptotic cell death plays a predominant role in histone deacetylase (HDAC) inhibitor-induced cytotoxicity. Nuclear morphological changes and activation of apoptotic executors are involved in CTS203-induced cell death. However, emerging issues of HDAC inhibitor-resistance have been observed in patients. Herein, MCF-7 cells were continuously exposed to CTS203 until the derived cells could proliferate normally in its presence. The newly obtained CTS203-resistant cells were nominated as MCF-7/203R. Compared to MCF-7 original cells, the MCF-7/203R cells were less sensitive to CTS203-induced apoptosis, with a minimal 6-fold higher IC50 value. In contrast, the expression of Beclin-1 was dramatically up-regulated, positively correlated to the acquisition of CTS203-resistance. Our results revealed the participation of autophagy in acquired HDAC inhibitor-resistance and further identified Beclin-1 as a promising target for anti-drug resistance.