Dihydromyricetin induces mitochondria-mediated apoptosis in HepG2 cells through down-regulation of the Akt/Bad pathway |
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| Institution: | 1. Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Rd, Ningbo, Zhejiang Province 315211, People''s Republic of China;2. Department of Clinical Nutrition, Ningbo Second Hospital, Ningbo, Zhejiang 315040, China;3. Hospital Infection-Control Department, Ningbo Medical Treatment Center, Lihuili Hospital, Ningbo, Zhejiang 315040, China;1. Medical School, Ningbo University, Ningbo, Zhejiang 315211, China;2. Nutrition Department, First People''s Hospital of Hangzhou, Hangzhou, Zhejiang 310006, China;3. Clinical Laboratory, Lihuili Hospital, Ningbo, Zhejiang 315040, China;4. Maritime Faculty, Ningbo University, Ningbo, Zhejiang 315211, China;5. Neurosurgery Department, Second Hospital of Ningbo, Ningbo, Zhejiang 315010, China;6. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, SAR 519000, China;7. Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA |
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| Abstract: | The plant flavonol dihydromyricetin (DHM) was reported to induce apoptosis in human hepatocarcinoma HepG2 cells. This study was undertaken to elucidate the underlying molecular mechanism of action of DHM. In the study, DHM down-regulated Akt expression and its phosphorylation at Ser473, up-regulated the levels of mitochondrial proapoptotic proteins Bax and Bad, and inhibited the phosphorylation of Bad at Ser136 and Ser112. It also inhibited the expression of the antiapoptotic protein Bcl-2 and enhanced the cleavage and activation of caspase-3 as well as the degradation of its downstream target poly(ADP-ribose) polymerase. Our results for the first time suggest that DHM-induced apoptosis in HepG2 cells may come about by the inhibition of the Akt/Bad signaling pathway and stimulation of the mitochondrial apoptotic pathway. Dihydromyricetin may be a promising therapeutic medication for hepatocellular carcinoma. |
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