Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells.
Phytother Res
; 31(10): 1529-1538, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28752532
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-ß-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. Copyright © 2017 John Wiley & Sons, Ltd.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quercetina
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Rutina
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Resistencia a Medicamentos Antineoplásicos
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Neoplasias de Mama Triplo Negativas
Limite:
Female
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Humans
Idioma:
En
Revista:
Phytother Res
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália