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Salinomycin (SAL) is a monocarboxylic polyether ionophore antibiotic isolated from  Streptomyces albus . It exhibits an effective antitumor potential against numerous human cancer cells. This study aimed to assess the antiproliferative effects of SAL in human hepatocellular carcinoma HepG2/C3a cell line. We investigated the effects of SAL on cell growth, DNA damage induction, cell cycle changes and apoptosis; and relative changes in expression of cell cycle-related, apoptosis-related, and CYP450 genes. SAL induced cell cycle arrest in the G2/M phase, upregulation of  CDKN1A  and  GADD45A  and downregulation of cyclin genes including  CCNB1  and  CCNA2.  SAL effectively suppressed mRNA levels of  CTNNB1  gene, an important oncogene that promotes tumorigenesis. The decrease of HepG2/C3A cells’ survival can also be due to downregulation of antiapoptotic  BCL-2  expression, thus promoting the induction of apoptosis by SAL. This study also demonstrated the ability of SAL in modulating hepatic cytochrome P450 (CYP) mRNA expression, such that SAL caused the upregulation of  CYP1A  members and  CYP3A5 ; and downregulation of  CYP3A4 . Taken together, these data contribute to the understanding of the mechanism of action of SAL, highlighting that metabolizing enzymes modulated by SAL can interfere with chemotherapy treatment and it must be considered in associated treatments.

Salinomycin induces cell cycle arrest and apoptosis and modulates hepatic cytochrome P450 mRNA expression in HepG2/C3a cells