Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism.
The development of antitumor chemotherapy drugs remains a key goal for oncologists, and natural products provide a vast resource for anti-cancer drug discovery. In the current study, we found that the flavonoid dihydromyricetin (DHM) exhibited antitumor activity against liver cancer cells, including primary cells obtained from hepatocellular carcinoma (HCC) patients. In contrast, DHM was not cytotoxic to immortalized normal liver cells. Furthermore, DHM treatment resulted in the growth inhibition and remission of xenotransplanted tumors in nude mice. Our results further demonstrated that this antitumor activity was caused by the activation of the p53-dependent apoptosis pathway via p53 phosphorylation at serine (15Ser). Moreover, our results showed that DHM plays a dual role in the induction of cell death when administered in combination with cisplatin, a common clinical drug that kills primary hepatoma cells but not normal liver cells.
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Qingyu
Q
Zhang
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Jie
J
Liu
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Bin
B
Liu
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Juan
J
Xia
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Nianping
N
Chen
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Xiaofeng
X
Chen
Laboratory of Molecular and Experimental Pathology, Key Laboratory of Animal Models and Human Disease Mechanisms of CAS and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China, Kunming 650223, China.
Yi
Y
Cao
Laboratory of Molecular and Experimental Pathology, Key Laboratory of Animal Models and Human Disease Mechanisms of CAS and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People's Republic of China, Kunming 650223, China.
Chen
C
Zhang
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Caijie
C
Lu
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Mingyi
M
Li
Key Laboratory of Hepatic Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Runzhi
R
Zhu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D044948:Flavonols / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000166:cytology / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D044948:Flavonols; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C472036:dihydromyricetin; D002945:Cisplatin