Mulberry leaf polyphenol extract induced apoptosis involving regulation of adenosine monophosphate-activated protein kinase/fatty acid synthase in a p53-negative hepatocellular carcinoma cell.
The polyphenols in mulberry leaf possess the ability to inhibit cell proliferation, invasion, and metastasis of tumors. It was reported that the p53 status plays an important role in switching apoptosis and the cell cycle following adenosine monophosphate-activated protein kinase (AMPK) activation. In this study, we aimed to detect the effect of the mulberry leaf polyphenol extract (MLPE) on inducing cell death in p53-negative (Hep3B) and p53-positive (Hep3B with transfected p53) hepatocellular carcinoma cells and also to clarify the role of p53 in MLPE-treated cells. After treatment of the Hep3B cells with MLPE, apoptosis was induced via the AMPK/PI3K/Akt and Bcl-2 family pathways. Transient transfection of p53 into Hep3B cells led to switching autophagy instead of apoptosis by MLPE treatment. We demonstrated that acridine orange staining and protein expressions of LC-3 and beclin-1 were increased in p53-transfected cells. These results implied induction of apoptosis or autophagy in MLPE-treated hepatocellular carcinoma cells can be due to the p53 status. We also found MLPE can not only activate AMPK but also diminish fatty acid synthase, a molecular target for cancer inhibition. At present, our results indicate MLPE can play an active role in mediating the cell death of hepatocellular carcinoma cells and the p53 might play an important role in regulating the death mechanisms.
School of Medical Laboratory and Biotechnology and ‡Institute of Biochemistry and Biotechnology, Chung-Shan Medical University , Taichung, Taiwan.
Tzi-Peng
TP
Yang
Huei-Jane
HJ
Lee
Ting-Tsz
TT
Ou
Ya-Ju
YJ
Chang
Chau-Jong
CJ
Wang
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D045744:Cell Line, Tumor; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D031625:Morus / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D010936:Plant Extracts; D059808:Polyphenols; D016159:Tumor Suppressor Protein p53; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D055372:AMP-Activated Protein Kinases