Quercetin, a bioflavonoid, inhibits the increase of human multidrug resistance gene (MDR1) expression caused by arsenite

Abstract

Expression of the MDRl gene, which encodes P-glycoprotein, is increased under some stress conditions. WC have repotted that quercedn. a bioflavonoid, inhibits the expression of heat-shock proteins. WC have identified the effects of quercetin on the MDRl gene expression in the human hepatocarcinoma cells line. HcpG?. The increase of P-glycoprolein synthesis and MDA/ mRNA accumulation caused by exposurL 1~ arscnite were inhibited by quercetin. The CAT assay suggested that quercctin suppressed the transcriptional activation of the MDRl gene after exposure to arseniLe. Although many drugs that prevent the Pglycoprotcin fumion have been reporlcd, this is the first report to describe the inhibition of MDR! expression by u leagent.

Quercetin, a Flavonol, Promotes Disassembly of Microtubules in Prostate Cancer Cells: Possible Mechanism of its Antitumor Activity.

“…In addition, the inhibitory actions of quercetin and genistein against multidrug resistant tumors, either in a p-glycoprotein mediated or in a non-pglycoprotein mediated manner, have been attracting the interest of many investigators [15,25,33,34]. Various observations, as described below, have been made to elucidate cytotoxic and differentiation properties of quercetin, genistein and their related flavonoids.…”

Rapid up-regulation of mdr1 expression by anthracyclines in a classical multidrug-resistant cell line

“…In contrast, mdrl expression has been shown to be rapidly inducible in human cell lines in response to heat shock, arsenite (Chin et al, 1990b;Kioka et al, 1992a) or differentiating agents Mickley et al, 1989). Using a CAT (chloramphenicol acetyltransferase) assay, the proximal promoter of the mdrl gene may be directly activated by some cytotoxic drugs (Kohno et al, 1989), as well as heat shock (Kioka et al, 1992b;Miyzaki et al, 1992), serum deprivation and differentiating agents Ferrandis and Benard, 1993).…”

Combination of Suboptimal Doses of Inhibitors Targeting Different Domains of LtrMDR1 Efficiently Overcomes Resistance of Leishmania spp. to Miltefosine by Inhibiting Drug Efflux

“…Cocktail 2, as previously shown with DNM, almost completely reversed its miltefosine resistance. A number of mammalian Pgp modulators, including the flavonoid quercetin, were found to decrease the expression of the transporter (22). In contrast, the miltefosine reversal effect observed with the cocktail of inhibitors was not related to any decrease in LtrMDR1 expression levels, as demonstrated by Western blot analysis with specific polyclonal antibodies against the transporter, in either the absence or the presence of the inhibitors (insert, Fig.…”