Differential effects of cisplatin combined with the flavonoid apigenin on HepG2, Hep3B, and Huh7 liver cancer cell lines

•The cell lines were differentially sensitized to APG and CDDP coadministration.•The mode of genotoxic action differed among cell lines.•APG and CDDP cotreatment induced a senescence-like phenotype in Hep3B and Huh7 cells.•APG enhanced CDDP’s anti-migratory and anti-invasive action. The potential of apigenin (APG) to enhance cisplatin’s (CDDP) chemotherapeutic efficacy was investigated in HepG2, Hep3B, and Huh7 liver cancer cell lines. The presence of 20 μM APG sensitized all cell lines to CDDP treatment (degree of sensitization based on the MTT assay: HepG2>Huh7>Hep3B). As reflected by sister chromatid exchange levels, the degree of genetic instability as well as DNA repair by homologous recombination differed among cell lines. CDDP and 20 μM APG cotreatment exhibited a synergistic genotoxic effect on Hep3B cells and a less than additive effect on HepG2 and Huh7 cells. Cell cycle delays were noticed during the first mitotic division in Hep3B and Huh7 cells and the second mitotic division in HepG2 cells. CDDP and CDDP + APG treatments reduced the clonogenic capacity of all cell lines; however, there was a discordance in drug sensitivity compared with the MMT assay. Furthermore, a senescence-like phenotype was induced, especially in Hep3B and Huh7 cells. Unlike CDDP monotherapy, the combined treatment exhibited a significant anti-invasive and anti-migratory action in all cancer cell lines. The fact that the three liver cancer cell lines responded differently, yet positively, to CDDP + APG cotreatment could be attributed to variations they present in gene expression. Complex mechanisms seem to influence cellular responses and cell fate.