DescriptionStilbenes are a class of compounds present in small fruits such as grapes and berries and are known to present diverse pharmacological properties which include cholesterol lowering, serum glucose regulation, controlling lifespan and anti-cancer activity. Resveratrol is one of the extensively studied stilbene. Pterostilbene (trans-3, 5-dimethoxy-4’-hydroxystilbene), a structural analog of resveratrol, is present in heartwood of the tree, Pterocarpus marsupium as well as in many small fruits such as blueberries.
In an attempt to study the effects of pterostilbene on colon carcinogenesis, we identified that pterostilbene inhibited expression of certain inflammatory genes in the colon and suppressed aberrant crypt foci formation in an azoxymethane (AOM)-induced model of colon carcinogenesis in rats. We also investigated the mechanism of anti-inflammatory action of pterostilbene using cultured HT-29 colon cancer cells. Our studies identified that the p38-ATF2 pathway was significantly inhibited by pterostilbene. More importantly, by silencing the expression of p38α isoform, there was significant reduction in iNOS and COX-2 induction. Interestingly, pterostilbene and the structurally similar compound, resveratrol, targeted different inflammatory pathways in HT-29 colon cells.
Pterostilbene given at 40 ppm of the diet of AOM-injected rats lowered the tumor multiplicity of non-invasive adenocarcinomas compared to the control diet. Pterostilbene lowered the β-catenin levels in HT-29 cells which can have implications in the action of the compound against cell proliferation. An evaluation of different structural analogs of pterostilbene revealed some compounds to have greater action than pterostilbene against colon cancer cells. Methoxylation, ester and amino modifications at the 4' position in the B ring conferred greater potency for the molecule against cell proliferation and inflammation in vitro. Amino substitutions and methoxy modifications with trans configuration reduced tumor burden significantly in the HT-29 xenograft tumor model in SCID mice. These compounds were present at higher levels in the serum of the animals compared to the levels of other compounds. In conclusion, stilbenoid class of compounds has promising effects against proliferation and inflammation in both in vivo and in vitro models of colon carcinogenesis.