Journal Article

The resveratrol analog 4,4′-dihydroxy-<i>trans</i>-stilbene suppresses transformation in normal mouse fibroblasts and inhibits proliferation and invasion of human breast cancer cells

Cristina Maccario, Monica Savio, Daniela Ferraro, Livia Bianchi, Roberto Pizzala, Luca Pretali, Luca Forti and Lucia Anna Stivala

in Carcinogenesis

Volume 33, issue 11, pages 2172-2180
Published in print November 2012 | ISSN: 0143-3334
Published online July 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs244
The resveratrol analog 4,4′-dihydroxy-trans-stilbene suppresses transformation in normal mouse fibroblasts and inhibits proliferation and invasion of human breast cancer cells

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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.

Journal Article.  6982 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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