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Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target

Abstract

This study demonstrates that the flavonoid quercetin (Q), a plant-derived compound with low toxicity in vivo, greatly potentiates the growth-inhibitory activity of Adriamycin (ADR) on MCF-7 ADR-resistant human breast cancer cells. The effect of Q was dose-dependent at concentrations ranging between 1 and 10 μM. Since ADR resistance in these cells is associated with the expression of high levels of P-glycoprotein (Pgp), we evaluated the effect of Q and related flavonoids of Pgp activity in cytofluorographic efflux experiments with the fluorescent dye rhodamine 123 (Rh 123). Our results indicate that Q and 3-OMe Q (3′,4′,7-trimethoxyquercetin) but not the 3-rhamnosylglucoside of Q (rutin) inhibit the Pgp pump-efflux activity in a dose-related manner. Moreover, 10 μM Q reduces the expression of the immunoreactive Pgp in MCF-7 ADR-resistant cells as evaluated by cytofluorimetric assay. In conclusion, these findings provide a further biological basis for the potential therapeutic application of Q as an anticancer drug either alone or in combination with ADR in multidrug-resistant breast tumor cells.

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Author information

Correspondence to S. Mancuso.

Additional information

This work was partially supported by grants from MURST (60% and 40%) and CNR (Special Projects: A.C.R.O. 94.01098.PF 39); R. DeVincenzo and G. Ferrandina are recipients of fellowships from the Italian Association for Cancer Research (AIRC); M. Cianfriglia was partly supported by the AIDS research project (contract 720/P)

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Scambia, G., Ranelletti, F.O., Panici, P.B. et al. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemother. Pharmacol. 34, 459–464 (1994). https://doi.org/10.1007/BF00685655

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Key words

  • Quercetin
  • Adriamycin
  • Multidrug resistance
  • Human breast cancer cells