Effect of polyphenols from kiwi by-products (PKWP) on redox and metabolic homeostasis of HepG2 cells

Abstract

Polyphenols from kiwi by-products (PKWP) have been previously reported to have an inhibitory effect on cancer cells; but, the potential anti-cancer mechanism remains unknown. Metabolic alterations in cancer cells provide bioenergy and substances for uncontrolled proliferation and development, and interfering with the metabolic pathways has been regarded as effective in impeding cancer progression. Cancer cells are also characterised by a relatively higher level of oxidative stress and an enhanced antioxidant defence system, facilitating multiple stages of tumorigenesis. Anti-cancer mechanisms of PKWP based on metabolic and redox homeostasis in HepG2 cells were thus investigated in the present work. The results showed that PKWP effectively decreased HepG2 cell viability in a concentration-dependent manner. PKWP caused metabolic disorders in HepG2 cells, and significantly affected the content of about 32 metabolites. PKWP mainly inhibited saccharide synthesis and glycolysis, and restricted the utilisation of amino acids. PKWP stimulated ROS production, and caused lipid peroxidation, resulting in oxidative damage. PKWP also down-regulated the activities of T-SOD and CAT, and the level of GSH, and inhibited the protein expressions of HO-1 and COX-2, weakening the cellular antioxidant capacity. Thus, PKWP could exert prominent anti-cancer activity in HepG2 cells by disrupting metabolic homeostasis, and induction of oxidative stress. These findings will provide evidence for further elucidation of the anti-cancer mechanism of PKWP, and the potential application of PKWP as a natural ingredient in functional food, cosmetic, and pharmaceutical industries.