A novel combined resveratrol/berberine phytochemotheraputic using the HePG2 cell line as a model for the treatment of hepatocarcinoma

The results presented herein show that at clinically relevant concentrations (0–30 µM), the well-tolerated phytochemical berberine (BER) induces cell death in cultured human hepatocarcinoma (HepG2) cells as a model for liver cancer, primarily via apoptosis. Similar, relatively low-concentration single treatments using the structurally related phytochemical resveratrol (RSV), had little or no effect on cell viability but inhibited the cell cycle, while simultaneously increasing the strength of cellular adhesion. When used in combination, an RSV/BER cotreatment appeared to retain the ability of a single RSV treatment to increase cellular adhesion, but also induced a massive loss in hepatocarcinoma cellular viability, inducing cell death in more than 90% of cells. This model, therefore, suggests that it may be possible to use RSV to stabilise hepatocarcinomas against metastasis while using cotreatment with BER to simultaneously induce cell death. By measuring the changes in the activity of the pleiotropic enzyme transglutaminase 2 (TGM2), which is known to be overexpressed in hepatocarcinoma and many other tumours, we hypothesise a role for this enzyme in the activities of these two phytochemicals, and propose the potential use of this RSV/BER cotreatment as a chemotherapeutic in TGM2+ hepatocarcinomas.