title: Involvement of autophagy in cordycepin-induced apoptosis in human prostate carcinoma LNCaP cells.
abstract: Cordycepin, an active ingredient of the insect fungus Cordyceps spp., shows strong antioxidant and anticancer activities. Several molecular mechanisms have been attributed to its inhibitory effects on a wide range of tumor cells; however, the mechanism causing cancer cell death is still obscure. For the current study, we further investigated the mechanism responsible for targeting cordycepin-induced cell death and its association with autophagy in human prostate carcinoma LNCaP cells. Our results show that cordycepin resulted in significant reduction in LNCaP cell survival by inducing apoptotic cell death. Cordycepin treatment caused a dose-dependent increase of pro-apoptotic Bax and decrease of anti-apoptotic Bcl-2, triggering collapse of the mitochondrial membrane potential and activation of caspase-9 and -3. Cordycepin-induced cell death was also associated with induction of Fas and death receptor 5, activation of caspase-8, and truncation of Bid (tBid), suggesting that tBid might serve to connect activation of both the mitochondrial-mediated intrinsic and death receptor-mediated extrinsic apoptotic pathways. The general caspase inhibitor, z-VAD-fmk, completely abolished cordycepin-induced cell death, demonstrating that cordycepin-induced apoptosis was dependent on the activation of caspases. Cordycepin also stimulated autophagy, which was evidenced by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3-II, and elevation of autophagic flux; however, blockage of autophagic flux by the autophagic inhibitor bafilomycin A1 promoted cell-switching to apoptotic cell death. These findings suggest that cordycepin-induced autophagy functions as a survival mechanism and that autophagy is a potential strategy for treating prostate cancer that is resistant to pro-apoptotic therapeutics.
authors: Daegu Gyeongbuk Institute of Science & Technology, Daegu 711-873, Republic of Korea.
authors: Hye Hyeon
authors: HH
authors: Lee
authors: Team for Scientification of Korean Medical Intervention (BK21 Plus) & Department of Herbal Pharmacology, College of Korean Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors: Sung Ok
authors: SO
authors: Kim
authors: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors: Gi-Young
authors: GY
authors: Kim
authors: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Republic of Korea.
authors: Sung-Kwon
authors: SK
authors: Moon
authors: Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-763, Republic of Korea.
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Department of Biotechnology, Dong-A University, Busan 604-714, Republic of Korea.
authors: Yong Kee
authors: YK
authors: Jeong
authors: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714, Republic of Korea. Electronic address: yhyoo@dau.ac.kr.
authors: Young Hyun
authors: YH
authors: Yoo
authors: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-714, Republic of Korea; Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea. Electronic address: choiyh@deu.ac.kr.
authors: Yung Hyun
authors: YH
authors: Choi
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002277:Carcinoma; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003839:Deoxyadenosines / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D061945:Caspase Inhibitors; D003839:Deoxyadenosines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases; C058120:cordycepin
keywords: Apoptosis; Autophagy; Cordycepin; LNCaP cells