Dihydromyricetin Enhances the Chemo-Sensitivity of Nedaplatin via Regulation of the p53/Bcl-2 Pathway in Hepatocellular Carcinoma Cells.
Chemotherapy is an effective weapon in the battle against cancer. Nedaplatin (NDP) is an improved platinum-containing drug with lower cytotoxicity than other similar drugs. However, the repeated use of NDP results in substantial hepatocyte damage as well as drug resistance in hepatocellular carcinoma (HCC) cases. Therefore, the development of effective chemotherapy strategies that enhance tumor sensitivity to chemotherapeutics and reduce the secondary damage to liver cells is urgently needed. Dihydromyricetin (DHM), a natural flavonoid compound, has been shown to have antitumor activity with no obvious toxicity to normal cells in vitro and in vivo. In this study, DHM and NDP were combined to treat liver cancer cells; we found that DHM functions as a protector of normal cells compared with the use of NDP alone. In addition, the synergy of DHM with NDP enhanced the effect of NDP on the induction of HCC cell apoptosis. We found that the combination caused clear changes in the level of reactive oxygen species (ROS). Furthermore, we demonstrated that the combination of DHM and NDP activated the p53/Bcl-2 signaling pathway, which resulted in mitochondrial dysfunction and induced cell death and growth inhibition in HCC cells.
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Lianggui
L
Jiang
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Qingyu
Q
Zhang
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Hao
H
Ren
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Sheng
S
Ma
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
CaiJie
C
Lu
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Bin
B
Liu
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Jie
J
Liu
Department of Gastroenterology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
Jian
J
Liang
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Mingyi
M
Li
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, China.
Runzhi
R
Zhu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D044948:Flavonols / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; D044948:Flavonols; D009944:Organoplatinum Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C053989:nedaplatin; C472036:dihydromyricetin