Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells

Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumor cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (Pgp) on the surface of tumor cells, thereby reducing d...

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Main Authors: Anuchapreeda S., Leechanachai P., Smith M.M., Ambudkar S.V., Limtrakul P.-N.
Format: Article
Language:English
Published: 2014
Online Access:http://www.scopus.com/inward/record.url?eid=2-s2.0-0037103569&partnerID=40&md5=b5b534bea267f4f3056d4548f797b52a
http://www.ncbi.nlm.nih.gov/pubmed/12167476
http://cmuir.cmu.ac.th/handle/6653943832/733
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spelling th-cmuir.6653943832-7332014-08-29T09:02:02Z Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells Anuchapreeda S. Leechanachai P. Smith M.M. Ambudkar S.V. Limtrakul P.-N. Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumor cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (Pgp) on the surface of tumor cells, thereby reducing drug cytotoxicity. In this study, curcumin was tested for its potential ability to modulate the expression and function of Pgp in the multidrug-resistant human cervical carcinoma cell line KB-V1. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) showed that treatment with 1, 5, and 10μM curcumin for up to 72hr was able to significantly lower Pgp expression in KB-V1 cells. Curcumin (1-10μM) decreased Pgp expression in a concentration-dependent manner and was also found to have the same effect on MDR1 mRNA levels. The effect of curcumin on Pgp function was demonstrated by rhodamine 123 (Rh123) accumulation and efflux in Pgp-expressing KB-V1 cells. Curcumin increased Rh123 accumulation in a concentration-dependent manner (1-55μM) and inhibited the efflux of Rh123 from these cells, but did not affect the efflux of Rh123 from the wild-type drug-sensitive KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with an increased intracellular accumulation of Rh123. In addition, curcumin inhibited verapamil-stimulated ATPase activity and the photoaffinity labeling of Pgp with the prazosin analog [125I]iodoarylazidoprazosin in a concentration-dependent manner, demonstrating that curcumin interacts directly with the transporter. Thus, curcumin seems to be able to modulate the in vitro expression and function of Pgp in multidrug-resistant human KB-V1 cells. In summary, this study describes the duel modulation of MDR1 expression and Pgp function by the phytochemical curcumin, which may be an attractive new agent for the chemosensitization of cancer cells. © 2002 Elsevier Science Inc. All rights reserved. 2014-08-29T09:02:02Z 2014-08-29T09:02:02Z 2002 Article 00062952 10.1016/S0006-2952(02)01224-8 12167476 BCPCA http://www.scopus.com/inward/record.url?eid=2-s2.0-0037103569&partnerID=40&md5=b5b534bea267f4f3056d4548f797b52a http://www.ncbi.nlm.nih.gov/pubmed/12167476 http://cmuir.cmu.ac.th/handle/6653943832/733 English
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
language English
description Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumor cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (Pgp) on the surface of tumor cells, thereby reducing drug cytotoxicity. In this study, curcumin was tested for its potential ability to modulate the expression and function of Pgp in the multidrug-resistant human cervical carcinoma cell line KB-V1. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) showed that treatment with 1, 5, and 10μM curcumin for up to 72hr was able to significantly lower Pgp expression in KB-V1 cells. Curcumin (1-10μM) decreased Pgp expression in a concentration-dependent manner and was also found to have the same effect on MDR1 mRNA levels. The effect of curcumin on Pgp function was demonstrated by rhodamine 123 (Rh123) accumulation and efflux in Pgp-expressing KB-V1 cells. Curcumin increased Rh123 accumulation in a concentration-dependent manner (1-55μM) and inhibited the efflux of Rh123 from these cells, but did not affect the efflux of Rh123 from the wild-type drug-sensitive KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with an increased intracellular accumulation of Rh123. In addition, curcumin inhibited verapamil-stimulated ATPase activity and the photoaffinity labeling of Pgp with the prazosin analog [125I]iodoarylazidoprazosin in a concentration-dependent manner, demonstrating that curcumin interacts directly with the transporter. Thus, curcumin seems to be able to modulate the in vitro expression and function of Pgp in multidrug-resistant human KB-V1 cells. In summary, this study describes the duel modulation of MDR1 expression and Pgp function by the phytochemical curcumin, which may be an attractive new agent for the chemosensitization of cancer cells. © 2002 Elsevier Science Inc. All rights reserved.
format Article
author Anuchapreeda S.
Leechanachai P.
Smith M.M.
Ambudkar S.V.
Limtrakul P.-N.
spellingShingle Anuchapreeda S.
Leechanachai P.
Smith M.M.
Ambudkar S.V.
Limtrakul P.-N.
Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
author_facet Anuchapreeda S.
Leechanachai P.
Smith M.M.
Ambudkar S.V.
Limtrakul P.-N.
author_sort Anuchapreeda S.
title Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
title_short Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
title_full Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
title_fullStr Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
title_full_unstemmed Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
title_sort modulation of p-glycoprotein expression and function by curcumin in multidrug-resistant human kb cells
publishDate 2014
url http://www.scopus.com/inward/record.url?eid=2-s2.0-0037103569&partnerID=40&md5=b5b534bea267f4f3056d4548f797b52a
http://www.ncbi.nlm.nih.gov/pubmed/12167476
http://cmuir.cmu.ac.th/handle/6653943832/733
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