Apogossypolone, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro.
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.
Zhang
Xian-Qing
XQ
Department of Blood Transfusion, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Huang
Xiao-Feng
XF
Hu
Xing-Bin
XB
Zhan
Yong-Hua
YH
An
Qun-Xing
QX
Yang
Shi-Ming
SM
Xia
Ai-Jun
AJ
Yi
Jing
J
Chen
Rui
R
Mu
Shi-Jie
SJ
Wu
Dao-Cheng
DC
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000648:ultrastructure; D004354:Drug Screening Assays, Antitumor; D006072:Gossypol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C534401:apogossypolone; C025946:3-methyladenine; D000225:Adenine; D006072:Gossypol