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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

  • Original Articles
  • Quercetin, Adriamycin, Multidrug Resistance, Human Bleast Cancer Cells
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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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Authors and Affiliations

  1. Department of Histology, Catholic University, Rome, Italy

    F. O. Ranelletti

  2. Department of Pathology, Catholic University, Rome, Italy

    M. Piantelli

  3. Department of Hematology, Catholic University, Rome, Italy

    S. Bussa & C. Rumi

  4. Department of Immunology, I. S. S. Rome, Rome, Italy

    M. Cianfriglia

  5. Department of Gynecology, Catholic University, Largo A. Gemelli 8, I-00168, Rome, Italy

    G. Scambia, P. Benedetti Panici, R. De Vincenzo, G. Bonanno, G. Ferrandina & S. Mancuso

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  1. G. Scambia
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  4. R. De Vincenzo
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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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  • DOI: https://doi.org/10.1007/BF00685655

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