Modulation of paclitaxel transport by flavonoid derivatives in human breast cancer cells. Is there a correlation between binding affinity to NBD of P-gp and modulation of transport?

Bioorganic & Medicinal Chemistry
Radka VáclavíkováIvan Gut

Abstract

We have investigated the effect of 13 flavonoid derivatives on [(14)C]paclitaxel transport in two human breast cancer cell lines, the adriamycin-resistant NCI/ADR-RES and sensitive MDA-MB-435. For this study, we selected representatives of aurones, chalcones, flavones, flavonols, chromones, and isoflavones with known binding affinity toward nucleotide-binding domain (NBD2) of P-glycoprotein and for which no reported work is available regarding paclitaxel transport. Aurones CB-284, CB-285, CB-287, and ML-50 most effectively inhibited P-gp related transport in the resistant line in comparison with chalcones, flavones, flavonols, chromones, and isoflavone derivatives and accordingly increased the accumulation of [(14)C]paclitaxel and decreased its efflux. Those agents efficiently modulated paclitaxel transport in P-gp highly expressing resistant human breast cancer cells and they could increase the efficiency of chemotherapy in paclitaxel-resistant tumors. In contrast, the sensitive cell line responded reversely in that CB-284, CB-285, CB-287, and ML-50 significantly inhibited accumulation of [(14)C]paclitaxel and especially CB-287, which significantly stimulated its efflux. Some, but not all, of the data correlated with the bindi...Continue Reading

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Citations

Jun 15, 2007·Pakistan Journal of Biological Sciences : PJBS·Supawadee DaodeeTeruo Murakami
Jan 13, 2009·Advanced Drug Delivery Reviews·E NicolleA Di Pietro
Aug 30, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Hong-May SimMei-Lin Go
Feb 22, 2012·Biochimica Et Biophysica Acta·Massimiliano CuccioloniMauro Angeletti
Jul 6, 2017·Toxicology Mechanisms and Methods·Pathomwat WongrattanakamonSupat Jiranusornkul
Oct 3, 2018·Current Medicinal Chemistry·Jiahua CuiLarry M C Chow
Jul 10, 2020·Bioscience, Biotechnology, and Biochemistry·Hiroki KobayashiMinoru Yoshida
Jan 1, 2011·International Journal of Medicinal Chemistry·A B IvanovaJ Molnar
Oct 30, 2007·Bioorganic & Medicinal Chemistry·Xiao-Ling LiuMei-Lin Go
May 18, 2020·European Journal of Cell Biology·Vladimír ČermákJan Brábek

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