Tetrandrine Induces Apoptosis in HepG2 by Modulating Hippo Signalling Pathway
Tetrandrine Induces Apoptosis in HepG2 by Modulating Hippo Signalling Pathway
Fuling Wang1,2, Changlin Yue2, Hong Li2, Wenjing Yu1, Wenlan Li1* and Guosong Xin1*
ABSTRACT
Tetrandrine (TET) has been known to possess anti-cancer properties in wide variety of cancers, however, the underlying mechanism for hepatocellular carcinoma (HCC) have not been fully elucidated. We focused our investigation the effect of TET on programmed cell death and growth of HepG2 cancer cell live. TET was found to significantly inhibit the proliferation of HepG2 cells, with an half maximal inhibitory concentration (IC50) of 7.76 μmol/L. Fluorescence microscopy showed that after 48 h of TET exposure, the cells presented morphological alterations typical of apoptosis while normal cellular morphology was preserved in the control. Staining with propidium iodide (PI), followed by flow cytometry showed that following 48 h TET treatment at 3.75, 7.5, and 15 μmol/L, the rate of apoptosis in HepG2 was 5.1%, 19.7%, and 36.9%, respectively. Western blotting was done to study the effect of TET on the expression profile of proteins involved in Hippo signalling pathway. We observed that in response to 48 h incubation with TET, there was a significant upregulation of the expression levels of MST1 (mammalian sterile 20-like kinase 1), LATS1 (large tumor suppressor kinase 1), and P-YAP1 while the expression levels of YAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif) were downregulated. Taken together, these results indicated that the anti-cancer activity of TET on HepG2 cells may be due to the modulation of Hippo signalling pathway.
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