A Resveratrol Phenylacetamide Derivative Perturbs the Cytoskeleton Dynamics Interfering with the Migration Potential in Breast Cancer

Abstract

Chemotherapy is commonly used for cancer treatment, however the lack of selectivity on healthy cells and the development of resistance phenomena are the major issues. A better understanding of cancer genetics helped the development of new targeted anticancer treatments, which permit drug delivery with high specificity and lower toxicity. Moreover, the multi-target drug design concept represents the current trend for future drug research and development. Starting from good results previously obtained by our research group on the resveratrol (RSV) phenylacetamide derivative 2, which displayed an interesting anti-inflammatory and anti-proliferative activity towards the breast cancer cells MCF-7 and MDA-MB-231, we identified other features, as the ability to perturb the cytoskeleton dynamics and interfere with the migration and metastatic processes. In vitro and in silico studies demonstrate that the derivative 2 is a tubulin and actin polymerization inhibitor and an actin depolymerization promotor. In addition, it interferes with the metastatic potential in both the breast cancer cells, inhibiting the in vitro cell migration and decreasing the spheroids number. These promising results demonstrate that the RSV phenylacetamide derivative 2 could be an important starting point in the discovery and development of safer and more efficacy multi-targeted agents.