Screening, characterization, and in vitro-ROS dependent cytotoxic potential of extract from Ficus carica against hepatocellular (HepG2) carcinoma cells.

Liver cancer is one of the most frequent causes of cancer-related deaths worldwide. The current study sought to screen, for the first time, a Ficus carica variety from the Shandong province of China against hepatocellular (HepG2) cells. Crude extracts of F. carica with various polarities were prepared and screened against HepG2 cells. The acetone extract of the leaf (FLA) exhibited significant antiproliferative effects against HepG2 cells (IC 50 = 0.179 mg/mL) while producing the least toxicity on normal human umbilical vein endothelial cells (HUVECs). Biochemical evidence of apoptosis was confirmed by staining with DAPI and AO/EB. FLA also exhibited moderate anti-colonization potential against the population of HepG2 cells. It selectively arrested the cell cycle of HepG2 cells at the S phase and exerted anticancer activity by significantly increasing the reactive oxygen species (1.59 fold) inside the cells, which subsequently resulted in loss of the mitochondrial membrane potential as revealed by JC-1 probe assay. FLA downregulated the expression of tumor-promoter Transcription Factor (TP53), anti-apoptotic proteins (Bcl-2), and cell cycle regulatory kinases (CDK1, 5, 9) with respect to untreated cells for 24 h, 48 h, and 72 h. High-performance liquid chromatography (HPLC) of FLA revealed the presence of gallic acid and quercetin as major antiproliferative compounds along with trace amounts of rutin, luteolin, apigenin, benzoic acid, and β-sitosterol. Notably, our study showed FLA operating via novel mechanisms involving reactive oxygen species (ROS) generation and CDKs involvement in HepG2 cells. Thus, it suggests that FLA may be a potential source of new drugs in the treatment of liver cancer. [Display omitted] • Acetone based extract from Ficus carica proved most cytotoxic against HepG2 cells. • Extract proved least toxic against human umbilical derived vascular endothelial cells. • Upsurge of reactive oxygen species and inactivated mitochondrial membrane potential-modes of apoptosis. • Alleviation in TP53, Bcl-2 and CDK1, CDK5 and CDK9 genes; induction of apoptosis. • The gallic acid and quercetin found as major compounds in active extract. [ABSTRACT FROM AUTHOR]