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. (January 2015)

• Record Type: Journal Article
• Authors: Cilla, Antonio; Attanzio, Alessandro; Barberá, Reyes; Tesoriere, Luisa; Livrea, Maria A.
• Is Part Of: Journal of functional foods. Volume 12(2015)
• Page Start: 282
• Page End: 293
• Publication Date: 2015-01
• Subjects: Anti-proliferation -- Apoptosis -- β-Cryptoxanthin -- Caco-2 cells -- Phytosterols; MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- PARP poly (ADP-ribose) polymerase -- PI propidium iodide -- Ps mix phytosterols mixture -- RONS reactive oxygen nitrogen species -- β-Cx β-cryptoxanthin; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2014.12.001
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: β-cryptoxanthin and main dietary phytosterols decrease Caco-2 cell proliferation. Apoptotic effect performed at compatible physiological human serum levels. Intracellular Ca 2+ influx and increase of ROS levels as initial apoptosis triggers. No additive or synergistic effects have been observed in their action. Antiproliferation complements their cardiovascular and osteoporosis decreasing risk. Abstract: β-cryptoxanthin (β-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 β-Cx and/or main dietary Ps (β-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, mitochondrial depolarization and caspase 3-dependent PARP cleavage, with intracellular Ca 2+ influx and increase of RONS levels as initial triggers. Ps and β-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.