title: Dihydromyricetin induces mitochondria-mediated apoptosis in HepG2 cells through down-regulation of the Akt/Bad pathway.
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.
authors.affiliation: 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.
authors.forename: Zhuangwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 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; Department of Clinical Nutrition, Ningbo Second Hospital, Ningbo, Zhejiang 315040, China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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; Hospital Infection-Control Department, Ningbo Medical Treatment Center, Lihuili Hospital, Ningbo, Zhejiang 315040, China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Anjun
authors.initials: A
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liao
authors.affiliation: 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.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Zuquan
authors.initials: Z
authors.lastname: Zou
authors.affiliation: 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. Electronic address: zhangxiaohong1@nbu.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D032421:Ampelopsis / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D044948:Flavonols / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: C494819:BAD protein, human; C494826:BAX protein, human; D044948:Flavonols; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; C472036:dihydromyricetin
keywords: Akt/Bad signaling pathway; Apoptosis; Dihydromyricetin; HepG2 cells; Hepatocellular carcinoma; Mitochondrial apoptotic pathway