Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in mdr cells

Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in mdr cells

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ABSTRACT MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF), suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study, quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells. SIMILAR CONTENT BEING VIEWED BY OTHERS C0818, A NOVEL CURCUMIN DERIVATIVE, INDUCES ROS-DEPENDENT CYTOTOXICITY IN HUMAN HEPATOCELLULAR CARCINOMA CELLS IN VITRO VIA DISRUPTION OF HSP90 FUNCTION Article 06 April 2021 COMBINATION THERAPY WITH HSP90 INHIBITORS AND PIPERLONGUMINE PROMOTES ROS-MEDIATED ER STRESS IN COLON CANCER CELLS Article Open access 13 October 2023 DECREASED EXPRESSION OF FBXW7 BY ERK1/2 ACTIVATION IN DRUG-RESISTANT CANCER CELLS CONFERS TRANSCRIPTIONAL ACTIVATION OF MDR1 BY SUPPRESSION OF UBIQUITIN DEGRADATION OF HSF1 Article Open access 26 May 2020 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biochemistry, College of Medicine, Pusan National University, Korea Sun-Hee Kim Authors * Sun-Hee Kim View author publications You can also search for this author inPubMed Google Scholar * Gae-Sun Yeo View author publications You can also search for this author inPubMed Google Scholar * Young-Sun Lim View author publications You can also search for this author inPubMed Google Scholar * Chi-Dug Kang View author publications You can also search for this author inPubMed Google Scholar * Cheol-Min Kim View author publications You can also search for this author inPubMed Google Scholar * Byung-Seon Chung View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kim, SH., Yeo, GS., Lim, YS. _et al._ Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells. _Exp Mol Med_ 30, 87–92 (1998). https://doi.org/10.1038/emm.1998.13 Download citation * Published: 01 June 1998 * Issue Date: 01 June 1998 * DOI: https://doi.org/10.1038/emm.1998.13 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * multidrug resistance (mdr) * heat shock factor (HSF) * quercetin

ABSTRACT MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF),


suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation


of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study,


quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced


MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level


of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease


the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells. SIMILAR CONTENT BEING VIEWED BY OTHERS C0818, A NOVEL CURCUMIN


DERIVATIVE, INDUCES ROS-DEPENDENT CYTOTOXICITY IN HUMAN HEPATOCELLULAR CARCINOMA CELLS IN VITRO VIA DISRUPTION OF HSP90 FUNCTION Article 06 April 2021 COMBINATION THERAPY WITH HSP90


INHIBITORS AND PIPERLONGUMINE PROMOTES ROS-MEDIATED ER STRESS IN COLON CANCER CELLS Article Open access 13 October 2023 DECREASED EXPRESSION OF FBXW7 BY ERK1/2 ACTIVATION IN DRUG-RESISTANT


CANCER CELLS CONFERS TRANSCRIPTIONAL ACTIVATION OF MDR1 BY SUPPRESSION OF UBIQUITIN DEGRADATION OF HSF1 Article Open access 26 May 2020 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND


AFFILIATIONS * Department of Biochemistry, College of Medicine, Pusan National University, Korea Sun-Hee Kim Authors * Sun-Hee Kim View author publications You can also search for this


author inPubMed Google Scholar * Gae-Sun Yeo View author publications You can also search for this author inPubMed Google Scholar * Young-Sun Lim View author publications You can also search


for this author inPubMed Google Scholar * Chi-Dug Kang View author publications You can also search for this author inPubMed Google Scholar * Cheol-Min Kim View author publications You can


also search for this author inPubMed Google Scholar * Byung-Seon Chung View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS This is an


Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted


non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kim, SH., Yeo,


GS., Lim, YS. _et al._ Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells. _Exp Mol Med_ 30, 87–92 (1998). https://doi.org/10.1038/emm.1998.13


Download citation * Published: 01 June 1998 * Issue Date: 01 June 1998 * DOI: https://doi.org/10.1038/emm.1998.13 SHARE THIS ARTICLE Anyone you share the following link with will be able to


read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing


initiative KEYWORDS * multidrug resistance (mdr) * heat shock factor (HSF) * quercetin