Shifting of cell cycle arrest from the S-phase to G2/M phase and downregulation of EGFR expression by phytochemical combinations in HeLa cervical cancer cells.

Cervical cancer is a major human papillomavirus-related disease and is the fourth leading cause of death by cancer among women. Plants are an important source of anticancer compounds and many of them are currently used in the treatment of cancer. Several reports suggest the efficacy of plant-derived compounds increases when used in combination. This study was carried out to evaluate the effect of four plant-derived compounds such as curcumin (C), ellagic acid (E), quercetin (Q), and resveratrol (R) when used alone or in combinations using HeLa cervical cancer cells. All four phytocompounds showed effective cytotoxic activities in targeting HeLa cervical cancer cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. The selected phytocompound combinations C + E, C + Q, and Q + R work synergistically while the combination C + R shows additive effects. All four phytocompounds reduce cell migration as determined by in vitro wound-healing assay. The expression level of the epidermal growth factor receptor is significantly downregulated both in individual and combination. The flow cytometry analysis of cell cycle indicates that individual drugs curcumin, ellagic acid, quercetin, and resveratrol, each with 20 µM effectively arrested cell cycle at the S-phase while the combination of drugs (10 + 10 µM) at the G2/M phase.