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  • Title: Reversal of ABCB1-related Multidrug Resistance of Colonic Adenocarcinoma Cells by Phenothiazines.
    Author: Takács D, Csonka Á, Horváth Á, Windt T, Gajdács M, Riedl Z, Hajós G, Amaral L, Molnár J, Spengler G.
    Journal: Anticancer Res; 2015 Jun; 35(6):3245-51. PubMed ID: 26026084.
    Abstract:
    BACKGROUND: The most common mechanism that reduces the efficacy of anticancer agents is overexpression of ATP-binding cassette (ABC) drug transporters. Phenothiazines and structurally-related compounds can sensitize multidrug-resistant (MDR) cells to chemotherapeutics. MATERIALS AND METHODS: Phenothiazine derivatives were investigated regarding their anticancer and MDR-reversing effect on colonic adenocarcinoma cells. The anti-proliferative and cytotoxic effects of the derivatives were assessed by the thiazolyl blue tetrazolium bromide (MTT) method, the modulation of the ABCB1 activity was measured by rhodamine 123 accumulation assay using flow cytometry. RESULTS: All phenothiazines exhibited potent cytotoxic effect on the sensitive and MDR colon adenocarcinoma cell lines. The inhibition of the ABCB1 transporter was greater in the presence of the phenothiazine derivatives than for the known ABCB1 inhibitor verapamil. CONCLUSION: It can be concluded that these derivatives show synergism in the presence of doxorubicin and could have potential as ABCB1 inhibitors.
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