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
| Autor: | Fu Shun Yu, Jiun Long Yang, Shu Jen Chang, Jing Gung Chung, Meng Wei Lin, Chun Shu Yu, Jaw-Chyun Chen, Hsu Feng Lu |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Programmed cell death biology Health Toxicology and Mutagenesis Poly ADP ribose polymerase Autophagy General Medicine Management Monitoring Policy and Law Toxicology Cell biology Squamous carcinoma Tetrandrine 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Apoptosis 030220 oncology & carcinogenesis biology.protein Cytotoxic T cell Caspase |
| Zdroj: | Environmental Toxicology. 31:395-406 |
| ISSN: | 1520-4081 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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