Redox-dependent and independent mechanisms of selective pro- and anti-apoptotic activity of Georgian legumes crops extracts on Jurkat and MDCK cells

Abstract

Background: Possibilities of pharmacological regulation of apoptosis play an important role in the treatment of different diseases. Polyphenol-rich plant extracts, as well as isolated polyphenols, can regulate cell apoptosis primarily through intrinsic and extrinsic mechanisms of action and are the most intriguing and studied class of compounds that can be therapeutics for a wide range of common diseases, including cancer. Polyphenols are well known as powerful antioxidants, their action is also associated with pro-apoptotic function in various types of tumor cells.

The purpose of this study was to establish the anti-and pro-apoptotic activity of Georgian legume crops in model cellular systems.

Methods: Legume crop extracts (LCEs) were prepared in water-alcohol solute. Polyphenols content in the extracts was determined by Folin–Ciocalteu method, antiradical activity (AA) - according the comparative time of the 50% neutralization of 2,2-diphenyl-1-picrylhydrazyl (DPPH) cleavage.

Studies were carried out on human leukemic mature T (Jurkat) and normal epithelial MDCK cells lines. For modelling of oxida­tive stress, 30% hydrogen peroxide was used. LCEs were added to intact or incubated under oxidative stress conditions Jurkat and MDCK cells. Cells’ viability was determined by 3-(4,5-dimethyltiazol-2)-2,5-diphenyl-tetrazolium-bromide (MTT) test. Catalase and Superoxidedismutase (SOD) activity in cellular supernatant was measured by spectrophotometry.

Results: LCEs revealed selective pro- and antiapoptotic activity on the intact and incubated under oxidative stress conditions Jurkat and MDCK cells. The cytotoxic effect of LCEs on intact Jurkat and MDCK cells was independent of their AA and activity of enzymatic cellular antioxidant defense system.

The cytoprotective effect of LCEs on MDCK cells was realized through redox-dependent mechanisms and is associated both with the own AA of the extracts and with the stimulating effect of the extracts on the activity of enzymatic cellular antioxidant defense system, where catalase played a leading role. LCEs didn’t protect Jurkat cells from oxidative stress-induced apoptosis.

Conclusion: The obtained results allow us to conclude that in cancer chemotherapy the legume extracts might be combined with prooxidant drugs, in order to protect normal cells, but not the malignant ones, from their apoptosis-inducing effect. On the other hand, these extracts may protect non-malignant tissues/organs from various apoptosis-related disorders.