Anti-tumor Properties of cis-Resveratrol Methylated Analogues in Metastatic Mouse Melanoma Cells

Resveratrol (E-3,5,40-trihydroxystilbene) is apolyphenol found in red wine that has been shown to havemultiple anti-cancer properties. Although cis-(Z)- and trans-(E)-isomers of resveratrol occur in nature, the cis form is notbiologically active. However, methylation at key positionsof the cis form results in more potent anti-cancer properties.This study determined that synthetic cis-polymethoxystilbenes(methylated analogs of cis-resveratrol) inhibited cancer-related phenotypes of metastatic B16 F10 and nonmetastaticB16 F1 mouse melanoma cells. In contrast withcis- or trans-resveratrol and trans-polymethoxystilbenewhich were ineffective at 10 lM, cis-polymethoxystilbenesinhibited motility and proliferation of melanoma cells withlow micromolar specificity (IC50\10 lM). Inhibitoryeffects by cis-polymethoxystilbenes were significantlystronger with B16 F10 cells and were accompanied bydecreased expression of b-tubulin and pleckstrin homologydomain-interacting protein, a marker of metastatic B16 cells.Thus, cis-polymethoxystilbenes have potential as chemotherapeuticagents for metastatic melanoma.