Int J Biol Sci 2021; 17(15):4340-4352. doi:10.7150/ijbs.64675 This issue

Research Paper

Cepharanthine inhibits hepatocellular carcinoma cell growth and proliferation by regulating amino acid metabolism and suppresses tumorigenesis in vivo

Fan Feng1, Lianhong Pan1,2, Jiaqin Wu1, Lanqing Li3, Haiying Xu3, Li Yang1, Kang Xu3✉, Chunli Wang1✉

1. National Innovation and Attracting Talents “111” base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
2. Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, Chongqing 400030, China.
3. Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.

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Citation:
Feng F, Pan L, Wu J, Li L, Xu H, Yang L, Xu K, Wang C. Cepharanthine inhibits hepatocellular carcinoma cell growth and proliferation by regulating amino acid metabolism and suppresses tumorigenesis in vivo. Int J Biol Sci 2021; 17(15):4340-4352. doi:10.7150/ijbs.64675. Available from https://www.ijbs.com/v17p4340.htm

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Abstract

Graphic abstract

Cepharanthine (CEP), a natural compound extracted from Stephania cepharantha Hayata, has been found to have the potential to treat a variety of tumors in recent years. This study aims to evaluate the anti-hepatocellular carcinoma (HCC) effect of CEP and determine its in-depth mechanism. In this study, Hep3B and HCCLM3 cells were selected to evaluate the antitumor effects of CEP in vitro, whereas tumor xenograft in nude mice was performed to make in vivo anti-tumor assessment. RNA-sequence (RNA-seq) was used to identify possible molecular targets and pathways. Further, gas chromatography mass spectrometry (GC-MS) was performed to assess the differential metabolites involved in mediating the effect of CEP on the HCC cell line. Our results showed that CEP treatment resulted in the dose-dependent inhibition of cell viability, migration, and proliferation and could also induce apoptosis in HCC cells. RNA-seq following CEP treatment identified 168 differentially expressed genes (DEGs), which were highly enriched in metabolism-associated pathways. In addition, CEP down-regulated many metabolites through the amino acid metabolism pathway. In vivo experiment showed that CEP significantly suppressed tumor growth. Our results indicate that CEP has significant antitumor effects and has the potential to be a candidate drug for HCC treatment.

Keywords: Cepharanthine, Hepatocellular carcinoma, Metabolism, Apoptosis.