Abstract
The ubiquitin-proteasome pathway has been accepted as a promising target for cancer therapy, as it plays a vital role in cell cycle, function, and survival. In this research, in silico study by molecular docking predicted that Tetrandrine(TET), a compound from the roots of Stephenia tetrandra S Moore, could bind to the active site of the proteasome β5 subunit. In vitro assay proved that TET inhibits the chymotrypsin-like (CT) activity of purified human 20S proteasome in a dose-dependent manner with IC50 of 0.8 μmol/L. After exposed to TET for 24 h, the CT activity in human prostate cancer PC-3 cells was inhibited with IC50 of 35 μmol/L, and the ubiquited proteins were accumulated in dose-dependent manner. This inhibition was further proved by the accumulation of GFP-CL proteins, which is an indicator of proteasome inhibition in pEGFP-CL1 transferred PC-3 cells. The proteasomal activity inhibition by TET leads to apoptosis like morphological changes and activation of caspase-3 activity in dose-dependent manner in PC-3 cells. Based on these results, we suppose that TET is a proteasome inhibitor and induces cell apoptosis.
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Acknowledgments
This work was supported by the National Natural Science Foundation (20977007), and Program for New Century Excellent Talents in University (NCET-11-0581).
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Zhang, L. et al. (2014). Tetrandrine Inhibits Proteasomal Chymotrypsin-Like Activity and Induces Apoptosis in Human PC-3 Cells. In: Zhang, TC., Ouyang, P., Kaplan, S., Skarnes, B. (eds) Proceedings of the 2012 International Conference on Applied Biotechnology (ICAB 2012). Lecture Notes in Electrical Engineering, vol 250. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37922-2_74
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DOI: https://doi.org/10.1007/978-3-642-37922-2_74
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