Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 - and oxidative stress-induced apoptosis

beta-cryptoxanthin (beta-Cx) and phytosterols (Ps) have potential against different cancer types, including colon cancer. However, their combined action has not been reported so far. Human colon cancer Caco-2 cells were treated 24 h with beta-Cx and/or main dietary Ps (beta-sitosterol, campesterol and stigmasterol), alone or in combination, at concentrations compatible with physiological human serum levels. A decrease in cell viability due to apoptosis (rise in sub-G1 population and exposure of membrane phosphatidylserine) was accompanied with dephosphorylation of BAD, mitochonthial depolarization and caspase 3-dependent PARP cleavage, with intracellular Ca2+ influx and increase of RONS levels as initial triggers. Ps and beta-Cx, alone or in combination showed anti-proliferative activity against human colon adenocarcinoma Caco-2 cells through the mitochondrial pathway of apoptosis. No additive or synergistic effects were observed. The importance of bioactivity-guided assays with mixtures of dietary bioactive compounds to determine their eventual interactions in the functional food context is demonstrated. (C) 2014 Elsevier Ltd. All rights reserved.