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Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells

Multidrug resistance (MDR) is a major obstacle to the chemotherapeutic treatment of breast cancer. Germacrone, the main component of Rhizoma Curcuma, has been shown to possess antitumor, anti-inflammatory and immunomodulatory properties. The aim of the present study was to investigate the effect of...

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Autores principales: XIE, XIAO-HONG, ZHAO, HONG, HU, YUAN-YUAN, GU, XI-DONG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186325/
https://www.ncbi.nlm.nih.gov/pubmed/25289068
http://dx.doi.org/10.3892/etm.2014.1932
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author XIE, XIAO-HONG
ZHAO, HONG
HU, YUAN-YUAN
GU, XI-DONG
author_facet XIE, XIAO-HONG
ZHAO, HONG
HU, YUAN-YUAN
GU, XI-DONG
author_sort XIE, XIAO-HONG
collection PubMed
description Multidrug resistance (MDR) is a major obstacle to the chemotherapeutic treatment of breast cancer. Germacrone, the main component of Rhizoma Curcuma, has been shown to possess antitumor, anti-inflammatory and immunomodulatory properties. The aim of the present study was to investigate the effect of germacrone on MCF-7/Adriamycin (ADR) multidrug-resistant human breast cancer cells. The treatment of MCF-7/ADR cells with a combination of germacrone and ADR resulted in an increase in cytotoxicity compared with that of ADR alone, as determined using an MTT assay. Flow cytometric analysis revealed that germacrone promoted cell apoptosis in a dose-dependent manner, whilst treatment with germacrone plus ADR enhanced the apoptotic effect synergistically. Furthermore, the results from the western blot analysis demonstrated that augmenting ADR treatment with germacrone resulted in a reduction of anti-apoptotic protein expression levels (bcl-2) and enhancement of pro-apoptotic protein expression levels (p53 and bax) in MCF-7/ADR cells compared with the levels achieved by treatment with ADR alone. In addition, germacrone significantly reduced the expression of P-glycoprotein via the inhibition of the multidrug resistance 1 (MDR1) gene promoter. These findings demonstrate that germacrone has a critical role against MDR and may be a novel MDR reversal agent for breast cancer chemotherapy.
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spelling pubmed-41863252014-10-06 Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells XIE, XIAO-HONG ZHAO, HONG HU, YUAN-YUAN GU, XI-DONG Exp Ther Med Articles Multidrug resistance (MDR) is a major obstacle to the chemotherapeutic treatment of breast cancer. Germacrone, the main component of Rhizoma Curcuma, has been shown to possess antitumor, anti-inflammatory and immunomodulatory properties. The aim of the present study was to investigate the effect of germacrone on MCF-7/Adriamycin (ADR) multidrug-resistant human breast cancer cells. The treatment of MCF-7/ADR cells with a combination of germacrone and ADR resulted in an increase in cytotoxicity compared with that of ADR alone, as determined using an MTT assay. Flow cytometric analysis revealed that germacrone promoted cell apoptosis in a dose-dependent manner, whilst treatment with germacrone plus ADR enhanced the apoptotic effect synergistically. Furthermore, the results from the western blot analysis demonstrated that augmenting ADR treatment with germacrone resulted in a reduction of anti-apoptotic protein expression levels (bcl-2) and enhancement of pro-apoptotic protein expression levels (p53 and bax) in MCF-7/ADR cells compared with the levels achieved by treatment with ADR alone. In addition, germacrone significantly reduced the expression of P-glycoprotein via the inhibition of the multidrug resistance 1 (MDR1) gene promoter. These findings demonstrate that germacrone has a critical role against MDR and may be a novel MDR reversal agent for breast cancer chemotherapy. D.A. Spandidos 2014-11 2014-08-26 /pmc/articles/PMC4186325/ /pubmed/25289068 http://dx.doi.org/10.3892/etm.2014.1932 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
XIE, XIAO-HONG
ZHAO, HONG
HU, YUAN-YUAN
GU, XI-DONG
Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells
title Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells
title_full Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells
title_fullStr Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells
title_full_unstemmed Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells
title_short Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells
title_sort germacrone reverses adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186325/
https://www.ncbi.nlm.nih.gov/pubmed/25289068
http://dx.doi.org/10.3892/etm.2014.1932
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