Title: Molecular mechanism of suppression of MDR1 by puerarin from<i>Pueraria lobata via</i>NF-κB pathway and cAMP-responsive element transcriptional activity-dependent up-regulation of AMP-activated protein kinase in breast cancer MCF-7/adr cells
Abstract: Molecular Nutrition & Food ResearchVolume 54, Issue 7 p. 918-928 Research Article Molecular mechanism of suppression of MDR1 by puerarin from Pueraria lobata via NF-κB pathway and cAMP-responsive element transcriptional activity-dependent up-regulation of AMP-activated protein kinase in breast cancer MCF-7/adr cells Tran Thi Hien, Tran Thi Hien College of Pharmacy, Chosun University, Gwangju, Republic of Korea These authors contributed equally to this work.Search for more papers by this authorHyung Gyun Kim, Hyung Gyun Kim College of Pharmacy, Chosun University, Gwangju, Republic of Korea These authors contributed equally to this work.Search for more papers by this authorEun Hee Han, Eun Hee Han College of Pharmacy, Chosun University, Gwangju, Republic of KoreaSearch for more papers by this authorKeon Wook Kang, Keon Wook Kang [email protected] College of Pharmacy, Chosun University, Gwangju, Republic of KoreaSearch for more papers by this authorHye Gwang Jeong, Corresponding Author Hye Gwang Jeong [email protected] College of Pharmacy, Chosun University, Gwangju, Republic of Korea College of Pharmacy, Chungnam National University, Daejeon, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea Fax: +82-42-825-4936Search for more papers by this author Tran Thi Hien, Tran Thi Hien College of Pharmacy, Chosun University, Gwangju, Republic of Korea These authors contributed equally to this work.Search for more papers by this authorHyung Gyun Kim, Hyung Gyun Kim College of Pharmacy, Chosun University, Gwangju, Republic of Korea These authors contributed equally to this work.Search for more papers by this authorEun Hee Han, Eun Hee Han College of Pharmacy, Chosun University, Gwangju, Republic of KoreaSearch for more papers by this authorKeon Wook Kang, Keon Wook Kang [email protected] College of Pharmacy, Chosun University, Gwangju, Republic of KoreaSearch for more papers by this authorHye Gwang Jeong, Corresponding Author Hye Gwang Jeong [email protected] College of Pharmacy, Chosun University, Gwangju, Republic of Korea College of Pharmacy, Chungnam National University, Daejeon, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea Fax: +82-42-825-4936Search for more papers by this author First published: 05 July 2010 https://doi.org/10.1002/mnfr.200900146Citations: 49 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy and its inhibition is an effective way to reverse cancer drug resistance. In the present study, we investigated that puerarin, a natural isoflavonoid from Pueraria lobata, down-regulated MDR1 expression in MCF-7/adriamycin (MCF-7/adr), a human breast MDR cancer cell line. Puerarin treatment significantly inhibited MDR1 expression, MDR1 mRNA and MDR1 promoter activity in MCF-7/adr cells. The suppression of MDR1 was accompanied by partial recovery of intracellular drug accumulation, leading to increased toxicity of adriamycin and fluorescence of rhodamine 123, indicating that puerarin reversed the MDR phenotype by inhibiting the drug efflux function of MDR1. Moreover, nuclear factor κ-B activity and IκB degradation were inhibited by puerarin. Puerarin stimulated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase and glycogen synthase kinase-3β phosphorylation, but puerarin decreased cAMP-responsive element-binding protein phosphorylation. The puerarin-induced suppression of MDR1 expression was reduced by AMPK inhibitor (compound C). Furthermore, both MDR1 protein expression and the transcriptional activity of cAMP-responsive element (CRE) were inhibited by puerarin and protein kinase A/CRE inhibitor (H89). Taken together, our results suggested that puerarin down-regulated MDR1 expression via nuclear factor κ-B and CRE transcriptional activity-dependent up-regulation of AMPK in MCF-7/adr cells. Citing Literature Volume54, Issue7July 2010Pages 918-928 RelatedInformation
Publication Year: 2010
Publication Date: 2010-01-13
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 74
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