Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Carcinoma, Hepatocellular / metabolism*
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Cell Line, Tumor
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Drug Synergism
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Flavonols / pharmacology*
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Humans
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Liver Neoplasms / metabolism*
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Organoplatinum Compounds / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Antineoplastic Agents
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BCL2 protein, human
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Flavonols
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Organoplatinum Compounds
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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nedaplatin
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dihydromyricetin
Grants and funding
This study was supported by The Guangdong Medical College Youth Fund (Q2012017,QYZ received this funding); Outstanding master's thesis cultivation project of Guangdong Medical College (2014-12#, LGJ received this funding); Key Laboratory of Zhanjiang project (2013A402-4, MYL received this funding); competitive projects of Zhanjiang, secondary financial support project (2013-17# and -10#, RZZ and JL (RZZ and Jian Liang received this funding); The National Natural Science Funds 81041099 and Guangdong Province Natural Science Funds S2011010003750 (MYL received these fundings). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.