Ruthana date extract inhibited proliferation of human hepatocellular carcinoma (HepG2) cells by modulation of BAX gene.

ABSTRACT

Cancer response to chemotherapeutic agents and its side effects remain a challenge for the development of new anticancer compounds. Dates are consumed worldwide due to their high nutritional value. We investigated the cytotoxicity and expression of the proapoptotic BAX gene in human hepatocellular carcinoma (HepG2) cells treated with Ruthana date ethanolic extract (RDE). The RDE ingredients analyzed by GC/MS and HepG2 cells were treated with different concentrations of RDE for 24, 48, and 72 h. Cytotoxicity, cell viability, DNA fragmentation, and BAX expression were determined. The GC/MS analysis of RDE showed its high content of quercetin, myricetin kaempferol, thymine, and catechol as the most active ingredients. HepG2 treated with RDE showed a significant change in morphological characteristics related to cell death. The antiproliferative activity determined by WST-1 demonstrated that RDE significantly reduced cell viability. Cells treated with RDE (10-60 mg) showed gradual DNA fragmentation in a dose-dependent manner. Gene expression analysis showed upregulation of BAX at 30 mg/ml of RDE (p < 0.001). However, it showed downregulation at (40-60 mg/ml) as compared to control. Our findings indicated that RDE exert cytotoxicity against HepG2 cells due to its high content of flavonoids. This effect through DNA fragmentation and activation of the proapoptotic BAX gene.