Data di Pubblicazione:
2017
Citazione:
Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells / M. Iriti, R. Kubina, A. Cochis, R. Sorrentino, E.M. Varoni, A. Kabala-Dzik, B. Azzimonti, A. Dziedzic, L. Rimondini, R.D. Wojtyczka. - In: PHYTOTHERAPY RESEARCH. - ISSN 0951-418X. - 31:10(2017 Oct), pp. 1529-1538. [10.1002/ptr.5878]
Abstract:
Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P-gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple-negative breast cancer cells, successfully arresting cell cycle progression.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
breast cancer resistance protein (BCRP); cell cycle; multidrug resistance; P-glycoprotein (P-gp); quercetin 3-O-β-d-rutinoside; Pharmacology
Elenco autori:
M. Iriti, R. Kubina, A. Cochis, R. Sorrentino, E..M. Varoni, A. Kabala-Dzik, B. Azzimonti, A. Dziedzic, L. Rimondini, R.D. Wojtyczka
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