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- W2622547047 abstract "Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephania tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes. In addition, tetandrine induces cell death in a panel of apoptosis-resistant cell lines that are deficient for caspase 3, caspase 7, caspase 3 and 7, or Bax-Bak respectively. We also showed that tetrandrine-induced cell death is independent of necrotic cell death. Mechanistically, tetrandrine induces autophagy that depends on mTOR inactivation. Furthermore, tetrandrine induces autophagy in a calcium/calmodulin-dependent protein kinase kinase-(CaMKK- 5' AMP-activated protein kinase (AMPK) independent manner. Finally, by kinase profiling against 300 WT kinases and computational molecular docking analysis, we showed that tetrandrine is a novel PKC-inhibitor, which lead to autophagic induction through PKC- inactivation. This study provides detailed insights into the novel cytotoxic mechanism of an anti-tumor compound originated from the herbal plant, which may be useful in promoting autophagy mediated- cell death in cancer cells that are resistant to apoptosis." @default.
- W2622547047 created "2017-06-15" @default.
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- W2622547047 date "2017-06-08" @default.
- W2622547047 modified "2023-10-14" @default.
- W2622547047 title "Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms" @default.
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- W2622547047 doi "https://doi.org/10.3389/fphar.2017.00351" @default.
- W2622547047 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5462963" @default.
- W2622547047 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28642707" @default.
- W2622547047 hasPublicationYear "2017" @default.
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