Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-β pathway.
Dihydromyricetin (DHM) is a flavonoid compound which possesses potent antitumor activity. In the present study, it was demonstrated that DHM significantly inhibited proliferation and induced apoptosis in mouse hepatocellular carcinoma Hepal‑6 cells. Transforming growth factor β (TGF‑β) is recognized as a major profibrogenic cytokine and is therefore a common target for drugs in the treatment of liver disease. The present study aimed to investigate whether TGF‑β was involved in DHM‑triggered cell‑viability inhibition and apoptosis induction. An MTT assay was used to evaluate the viability of Hepal‑6 cells following DHM treatment. TGF‑β signalling is mediated by Smads and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a crucial regulator of reactive oxygen species ROS production. TGF‑β, Smad3, phosphorylated (p)‑Smad2/3 and NOX4 protein expression levels were evaluated by western blot analysis. TGF‑β and NOX4 gene expression levels were determined by quantitative polymerase chain reaction. The results indicated that DHM downregulated TGF‑β, Smad3, p‑Smad2/3 and NOX4 in a concentration‑dependent manner. A cell counting assay indicated that DHM also inhibited Hepal‑6 cell growth in a concentration‑dependent manner. TGF‑β expression was significantly decreased following DHM treatment. In conclusion, the results of the present study defined and supported a novel function for DHM, indicating that it induced cell apoptosis by downregulating ROS production via the TGF‑β/Smad3 signaling pathway in mouse hepatocellular carcinoma Hepal‑6 cells.
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Bin
B
Liu
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Wei
W
Zhou
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Xiaofeng
X
Chen
Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Fengming
F
Xu
Department of Interventional Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Yinqin
Y
Chen
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Jie
J
Liu
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Qingyu
Q
Zhang
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Shiting
S
Bao
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Nianping
N
Chen
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Mingyi
M
Li
Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Runzhi
R
Zhu
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044948:Flavonols / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D044948:Flavonols; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D000255:Adenosine Triphosphate; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; C472036:dihydromyricetin