Enhanced Combinatorial Effect of Resveratrol in Conjunction with other Naturally Occurring Bioactive Compounds

Optimal diet is critical for a healthy life, and, for example, the Mediterranean diet has been associated with a wide range of benefits for overall health. Specific links have been made to anti-cancer effects of the Mediterranean diet through reducing oxidative and inflammatory processes and reducing cell proliferation. In the present study, we aimed to understand the effect of specific dietary compounds on colorectal cancer cell proliferation. As humans are seldom exposed to high concentrations of single bioactive compounds through the diet but rather, multiple compounds at low concentrations, we investigated the combined effect of bioactive compounds at low concentrations. While a combination of four structurally related stilbenoids (resveratrol, pterostilbene, piceatannol and oxyresveratrol) had antagonistic to additive effects on inhibition of cell proliferation, a combination of four structurally diverse compounds (resveratrol, curcumin, 3,3′-diindolylmethane and artemisinin) resulted in synergistic to additive effects. Taken together, these result show that a mixture of four dietary bioactive compounds have a significant inhibitory potential on cell proliferation, even at low concentrations, and support the notion of cancer risk reduction associated with the Mediterranean diet being due to a combination of chemopreventive compounds.