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A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth
Authors:Adele Chimento  Anna Santarsiero  Domenico Iacopetta  Jessica Ceramella  Arianna De Luca  Vittoria Infantino  Ortensia Ilaria Parisi  Paola Avena  Maria Grazia Bonomo  Carmela Saturnino  Maria Stefania Sinicropi  Vincenzo Pezzi
Affiliation:1.Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Arcavacata di Rende, 87036 Cosenza, Italy; (D.I.); (J.C.); (A.D.L.); (O.I.P.); (P.A.); (M.S.S.);2.Department of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, Italy; (A.S.); (V.I.); (M.G.B.);3.Spinoff TNcKILLERS, Viale dell’Ateneo Lucano 10, 85100 Potenza, Italy
Abstract:Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.
Keywords:resveratrol   phenylacetamide RSV derivatives   breast cancer cell lines   antiproliferative activity   anti-inflammatory activity   cell cycle arrest   cell death
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