Anti-proliferative and anti-metastasis effects of ten oligostilbenes from the seeds of Paeonia suffruticosa on human cancer cells

Paeonia suffruticosa from the section Moutan of the genus Paeonia is an important Chinese medicinal herb. In our previous study, 10 oligostilbenes from the seeds of P. suffruticosa, including trans-resveratrol and its dimers and trimers, were isolated and identified. In the present study, the anti-proliferative effects of these 10 oligostilbenes were systemically evaluated in a panel of human lung, breast and bone cancer cell lines, and their apoptotic effects were analyzed using a high-content multiplex apoptosis assay and a fluorescent caspase-3/7 assay. Furthermore, their anti-metastasis effects were examined in an invasive breast cancer cell line. Among the ten compounds, two resveratrol dimers, trans- and cis-gnetin H, showed the most potent anti-proliferative and anti-metastasis effects. All trans-oligostilbenes were more effective than their cis-forms, and trimers of resveratrol were more effective than dimers and the resveratrol isomer. The structure-activity relationships revealed that the polymerization degree, the double bond in the stilbene skeleton, and the steric arrangement and conformation of oligostilbenes obviously affected their antitumor potential. The results from this study provide valuable information for future semi-synthesis of resveratrol derivatives to develop novel cancer chemopreventive agents.