title: The interplay between autophagy and apoptosis induced by tanshinone IIA in prostate cancer cells.
abstract: Tanshinone IIA (T2A), a derivative of phenanthrenequinone and also the major active ingredient of Danshen, has been paid extensive attention as a promising cancer therapy for its potential anti-cancer activities. In this study, the apoptosis and autophagy of human prostate cancer PC-3 cells were observed after 5 μM T2A treatment, as well as their relevance. Mitochondrial-dependent apoptosis was firstly detected through morphological observation and biochemical analysis. Meanwhile, 5 μM T2A successfully triggered the autophagy of PC-3 cells, indicated by increased expression of Beclin1, and LC3 II. Validation experiments were conducted to further consolidate T2A's contribution to autophagy: Pretreatment with autophagy inhibitor 3-methyladenine (3-MA) provided protection against autophagy and enhanced T2A-induced apoptosis. Besides, the apoptosis suppressor z-VAD-fmk failed to facilitate the formation of autophagic vacuoles, which also proved the T2A-induced autophagy independent of apoptosis. Moreover, the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) efficiently inhibited the expression of Beclin1, LC3-II, and cleaved caspase-3, which indicated apoptosis and autophagy with dependence on intracellular ROS production. Taken together, these results demonstrated that autophagy is the cytoprotective mechanism in this experimental system, and the ROS resulted from T2A treatment played a critical role in apoptosis and autophagy initiation.
authors.affiliation: Urological Department, Affiliate Hospital of Weifang Medical University, No.2428 Yuhe Road, Weifang, Shandong, China. li_cl88@126.com.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Li
authors.affiliation: Urological Department, Affiliate Hospital of Weifang Medical University, No.2428 Yuhe Road, Weifang, Shandong, China.
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Han
authors.affiliation: Urological Department, Affiliate Hospital of Weifang Medical University, No.2428 Yuhe Road, Weifang, Shandong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Urological Department, Affiliate Hospital of Weifang Medical University, No.2428 Yuhe Road, Weifang, Shandong, China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Urological Department, Affiliate Hospital of Weifang Medical University, No.2428 Yuhe Road, Weifang, Shandong, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Li
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology; D000230:Adenocarcinoma / Q000473:pathology*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000096:biosynthesis / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045784:Abietanes; D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C021751:tanshinone; C505407:CASP3 protein, human; D053148:Caspase 3; D000111:Acetylcysteine
keywords: Apoptosis; Autophagy; Prostate cancer; Reactive oxygen species; Tanshinone IIA