Resveratrol Analogs and Prodrugs Differently Affect the Survival of Breast Cancer Cells Impairing Estrogen/Estrogen Receptor α/Neuroglobin Pathway.

Content Provider	Europe PMC
Author	Montalesi, Emiliano Cracco, Patrizio Acconcia, Filippo Fiocchetti, Marco Iucci, Giovanna Battocchio, Chiara Orlandini, Elisabetta Ciccone, Lidia Nencetti, Susanna Muzzi, Maurizio Moreno, Sandra Venditti, Iole Marino, Maria
Editor	Chung, Hwan-Suck
Copyright Year	2023
Abstract	Breast cancer is the first leading tumor in women in terms of incidence worldwide. Seventy percent of cases are estrogen receptor (ER) α-positive. In these malignancies, 17β-estradiol (E2) via ERα increases the levels of neuroglobin (NGB), a compensatory protein that protects cancer cells from stress-induced apoptosis, including chemotherapeutic drug treatment. Our previous data indicate that resveratrol (RSV), a plant-derived polyphenol, prevents E2/ERα-induced NGB accumulation in this cellular context, making E2-dependent breast cancer cells more prone to apoptosis. Unfortunately, RSV is readily metabolized, thus preventing its effectiveness. Here, four different RSV analogs have been developed, and their effect on the ERα/NGB pathway has been compared with RSV conjugated with highly hydrophilic gold nanoparticles as prodrug to evaluate if RSV derivatives maintain the breast cancer cells' susceptibility to the chemotherapeutic drug paclitaxel as the original compound. Results demonstrate that RSV conjugation with gold nanoparticles increases RSV efficacy, with respect to RSV analogues, reducing NGB levels and enhancing the pro-apoptotic action of paclitaxel, even preventing the anti-apoptotic action exerted by E2 treatment on these cells. Overall, RSV conjugation with gold nanoparticles makes this complex a promising agent for medical application in breast cancer treatment.
Journal	International Journal of Molecular Sciences [Int J Mol Sci]
Volume Number	24
DOI	10.3390/ijms24032148
PubMed Central reference number	PMC9916867
Issue Number	3
PubMed reference number	36768470
e-ISSN	14220067
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2023-01-21
Access Restriction	Open
Subject Keyword	breast cancer cells estrogen receptor α resveratrol resveratrol analogs gold nanoparticles
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Molecular Biology Spectroscopy Catalysis Computer Science Applications Medicine Inorganic Chemistry Organic Chemistry