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

Abstract

Cepharanthine (CEP), a natural compound extracted from <i>Stephania cepharantha</i> 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 <i>in vitro</i>, whereas tumor xenograft in nude mice was performed to make <i>in vivo</i> 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. <i>In vivo</i> 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.