RESUMEN
Flavonoids have a pivotal cytotoxic effect against hepatocellular carcinoma (HCC). The current study aimed to investigate which flavonoid isolated from Physalis pubescens L. leaves has the most cytotoxic effect against Hep-G2 liver cancer cells and if it could ameliorate epirubicin efficacy and safety. Baicalein trimethyl ether (BTME), rutin, quercitrin and myricitrin were isolated from Physalis Pubescens L. leaves. Hep-G2 cells were treated with the isolated flavonoids as well as a combination of BTME and epirubicin. Cell viability and the chromosomal DNA fragmentation in Hep-G2 cells were assessed. BTME showed the best cytotoxic effect against Hep-G2 cells. Combination of epirubicin with (200 µg/mL) BTME significantly decreased the IC50 of epirubicin from 2.79 ± 0.626 µg/mL to 0.76 ± 0.258 µg/mL. Moreover, the same combination significantly increased the IC50 of BTME against WI-38 normal cells. DNA fragmentation as well as the concentration of beclin 1 and Bax were significantly increased in Hep-G2 cells treated with BTME and BTME+epirubicin compared to untreated cells. Besides, BTME and BTME+epirubicin significantly decreased the gene expression of TGFß1 whereas increased ATG-7 gene expression. Conclusions: BTME (200µg/mL) significantly enhanced epirubicin's cytotoxicity against Hep-G2 cells and ameliorated its safety profile. BTME could exert anti-hepatocarcinoma effect by enhancing apoptosis and autophagy.