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Abstract

Volume 12, Issue 5 (September 2010) 12, 697–708; 10.1038/aja.2010.57

Apogossypolone, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro

Xian-Qing Zhang1,*, Xiao-Feng Huang2,*, Xing-Bin Hu1, Yong-Hua Zhan3, Qun-Xing An1, Shi-Ming Yang4, Ai-Jun Xia1, Jing Yi1, Rui Chen1, Shi-Jie Mu1 and Dao-Cheng Wu5

1 Department of Blood Transfusion, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
2 Central Laboratory, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China
3 School of Life Sciences and Technology, Xidian University, Xi’an 710071, China
4 Department of Blood Transfusion, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
5 The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, Xi’an Jiaotong University, Xi’an 710038, China

* These authors contributed equally to this work.

Correspondence: Prof. Dao-Cheng Wu,wudaocheng@mail.xjtu.edu.cn;Prof. Shi-Jie Mu,sxkhla@mail.xjtu.edu.cn

Received 9 February 2010; Revised 21 April 2010; Accepted 1 June 2010; Published online 26 July 2010.

Abstract

Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkylating agents, diminish multidrug resistance and decrease metastasis. Whether or not it can induce autophagy in cancer cells has not yet been determined. Here we investigated the antiproliferative activity of apogossypolone (ApoG2) and (−)-gossypol on the human prostate cancer cell line PC3 and LNCaP in vitro. Exposure of PC-3 and LNCaP cells to ApoG2 resulted in several specific features characteristic of autophagy, including the appearance of membranous vacuoles in the cytoplasm and formation of acidic vesicular organelles. Expression of autophagy-associated LC3-II and beclin-1 increased in both cell lines after treatment. Inhibition of autophagy with 3-methyladenine promoted apoptosis of both cell types. Taken together, these data demonstrated that induction of autophagy could represent a defense mechanism against apoptosis in human prostate cancer cells.


Keywords:

apogossypolone; apoptosis; autophagy; prostate cancer

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