4,4'-dihydroxy-trans-stilbene (DHS) is a synthetic analog of
resveratrol, a phytoalexin known for its
biological activities. We previously demonstrated that DHS exerts an antiproliferative effect on normal human fibroblasts that is higher than that of the natural parent molecule. No evidence regarding its role in human
cancer cell lines has been found thus far. In this study, we investigated the effects of DHS both on chemical-induced transformation of BALB/c 3T3 mouse fibroblasts and on the proliferation and invasion of human
breast cancer MCF-7 cells. The results showed that DHS markedly suppresses the two-stage (3-methylcholanthrene plus 12-O-tetradecanoylphorbol-13-acetate) cell transformation. Compared with
resveratrol, DHS inhibited both anchorage-dependent and -independent MCF-7 growth more efficiently. In addition, a reduction in the number of cells in S-phase, characterized by a concomitant increase in the levels of p21 and p53
proteins, together with a strong inhibition of pRb
protein phosphorylation, was observed in DHS-treated cells. Furthermore, DHS effected a strong reduction in
matrix metalloproteinase-2 and -9 activities, concomitantly with a marked inhibition of cell adhesion to the extracellular matrix components as well as inhibition of cell migration and invasion. Importantly, modulation of the adhesion molecule
E-cadherin was also found in DHS-treated cells. Taken together, these results demonstrate that the two 4,4'-hydroxyl groups on the stilbenic backbone make DHS a more active molecule than
resveratrol in inhibiting neoplastic transformation,
cancer cell proliferation and invasion. In conclusion, this study suggests that DHS could be a promising
anticancer agent.