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...

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Published in:Environmental toxicology 2016-04, Vol.31 (4), p.395-406
Main Authors: Yu, Fu-Shun, Yu, Chun-Shu, Chen, Jaw-Chyun, Yang, Jiun-Long, Lu, Hsu-Feng, Chang, Shu-Jen, Lin, Meng-Wei, Chung, Jing-Gung
Format: Article
Language:English
Subjects:
apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Apoptosis Regulatory Proteins - metabolism
autophagy
Autophagy - drug effects
Autophagy - physiology
Beclin-1
Benzylisoquinolines - pharmacology
Caspase 3 - metabolism
Caspase 8 - metabolism
Caspase 9 - metabolism
Cell Line, Tumor
DNA Fragmentation
HSC-3 cell line
Humans
Membrane Proteins - metabolism
Microtubule-Associated Proteins
Mouth Neoplasms - drug therapy
Mouth Neoplasms - metabolism
oral cancer
Poly(ADP-ribose) Polymerases - metabolism
Signal Transduction
tetrandrine
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Summary: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. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 395–406, 2016.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.22053