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Abstract Title:

Synergistic effects ofα-Mangostin and sorafenib in hepatocellular carcinoma: New insights into α-mangostin cytotoxicity.

Abstract Source:

Biochem Biophys Res Commun. 2021 Jun 18 ;558:14-21. Epub 2021 Apr 22. PMID: 33894673

Abstract Author(s):

Tian-Tian Wang, Ying-Fen Hong, Zhan-Hong Chen, Dong-Hao Wu, Yang Li, Xiang-Yuan Wu, Hui-Qiang Huang, Qi Zhang, Chang-Chang Jia

Article Affiliation:

Tian-Tian Wang

Abstract:

Sorafenib remains the standard first-line treatment for advanced hepatocellular carcinoma (HCC), although other clinical trials are currently underway for treatments that show better curative effects. However, some patients are not sensitive to sorafenib.α-Mangostin, extracted from the pericarp of the mangosteen, which is widely used as a traditional medicine, has anticancer and anti-proliferative properties in various types of cancers, including HCC. In the present study, we found that combining sorafenib and α-Mangostin could be synergisticallytoxic to HCC both in vitro and in vivo. We then demonstrated that the combination of sorafenib and α-Mangostin enhances the inhibition of cell proliferation in HCC cell lines. Combination therapy leads directly to apoptosis. In xenograft mouse models, the in vivo safety and effectivity was confirmed by a reduction in tumor size after combination treatment. RNA sequencing and protein testing showed that the expression of LRRC8A and RNF181 genes and mTOR and MAPK pathways may be associated with the synergistic effect of the two drugs. In conclusion, our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.

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