title: Tetrandrine induces apoptosis Via caspase-8, -9, and -3 and poly (ADP ribose) polymerase dependent pathways and autophagy through beclin-1/ LC3-I, II signaling pathways in human oral cancer HSC-3 cells.
abstract: Tetrandrine is a bisbenzylisoquinoline alkaloid that was found in the Radix Stephania tetrandra S Moore. It had been reported to induce cytotoxic effects on many human cancer cells. In this study, we investigated the cytotoxic effects of tetrandrine on human oral cancer HSC-3 cells in vitro. Treatments of HSC-3 cells with tetrandrine significantly decreased the percentage of viable cells through the induction of autophagy and apoptosis and these effects are in concentration-dependent manner. To define the mechanism underlying the cytotoxic effects of tetrandrine, we investigated the critical molecular events known to regulate the apoptotic and autophagic machinery. Tetrandrine induced chromatin condensation, internucleosomal DNA fragmentation, activation of caspases-3, -8, and -9, and cleavage of poly (ADP ribose) polymerase (PARP) that were associated with apoptosis, and it also enhanced the expression of LC3-I and -II that were associated with the induction of autophagy in human squamous carcinoma cell line (HSC-3) cells. Tetrandrine induced autophagy in HSC-3 cells was significantly attenuated by bafilomycin A1 (inhibitor of autophagy) pre-treatment that confirmed tetrandrine induced cell death may be associated with the autophagy. In conclusion, we suggest that tetrandrine induced cell death may be through the induction of apoptosis as well as autophagy in human oral cancer HSC-3 cells via PARP, caspases/Becline I/LC3-I/II signaling pathways.
authors.affiliation: Department of Dentist, China Medical University, Taichung, 404, Taiwan.
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Yu
authors.affiliation: Department of Medicinal Botany and Health Applications, Da-Yeh University, Changhua, Taiwan.
authors.forename: Jaw-Chyun
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Chinese Medicine Resources, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jiun-Long
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan.|School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, Yilan, Taiwan.
authors.forename: Meng-Wei
authors.initials: MW
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D000071186:Beclin-1; D044182:Benzylisoquinolines / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D044182:Benzylisoquinolines; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C009438:tetrandrine; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: HSC-3 cell line; apoptosis; autophagy; oral cancer; tetrandrine