trans-Resveratrol has beneficial effects on colorectal cancer, through its antioxidant capacity, and its roles in regulating eicosanoid synthesis. This study determines how changes in resveratrol structure affected its biological activities. Our results showed that trans- and cis-resveratrol and hydroxylated analogs (piceatannol) (10-25 μM) displayed similar antioxidant activities (2-3 fold higher than trolox) and inhibit eicosanoid synthesis and Caco-2 growth (76.5 ± 2.7%, 48.2 ± 3.1% and 41.1 ± 2.3%, p ≤ 0.05). These effects can be related with an increase of the percentage of cells in the S phase (156.3 ± 5.6, 91.2 ± 3.3 and 64.1 ± 2.8, p ≤ 0.05) as a consequence of the impairment of the cells in G0/G1. Furthermore, we observed that these molecules induce apoptosis at 100 μM (48.2 ± 6.6%, p ≤ 0.05; 4.3 ± 2.5% and 21.2 ± 3.3%, p ≤ 0.05). These actions were related with changes of the mitochondrial membrane potential involved in the intrinsic pathway of apoptosis. However, methoxylated (pterostilbene, pinostilbene, trans-trimethoxy-resveratrol, and CAY10616) (0.1-10 μM) and halogenated (PDM11, CAY10464, PDM2, and CAY465) (1-10 μM) stilbenes inhibited Caco-2 cell growth, with a higher potency than resveratrol (50% inhibition at 0.1-1 μM) but without effects on oxidative stress and arachidonic acid cascade. Thus, our results show that the antioxidant effect of hydroxyl stilbenes is related to eicosanoid synthesis regulation and the basic stilbene structure of two benzene rings bonded through a central ethylene, is responsible for its effects on Caco-2 cell growth/DNA synthesis/cell cycle independently of redox state/eicosanoid synthesis modulation.
Keywords: apoptosis; colorectal cancer; eicosanoid; polyphenol; prostaglandin.