| Key structure of Brij for overcoming multidrug resistance in cancer. | |
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MedLine Citation:
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PMID: 23311629 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Multidrug resistance (MDR) is a major barrier to the chemotherapy treatment of many cancers. However, some non-ionic surfactants, for example Brij, have been shown to restore the sensitivity of MDR cells to such drugs. The aim of this study was to explore the reversal effect of Brij on MDR tumor cells and elucidate its potential mechanism. Our data indicate that the structure of Brij surfactants plays an important role in overcoming MDR in cancer, i.e. modified hydrophilic-lipophilic balance (MHLB, the ratio of the number (n) of hydrophilic repeating units of ethylene oxide (EO) to the number (m) of carbons in the hydrophobic tail (CH2).). Cell viability of cells treated with paclitaxel (PTX) nanocrystals (NCs) formulated with Brij showed positive correlations with MHLB (R2 = 0.8195); the higher the ratio of Brij to PTX in NCs, the higher cytotoxicity induced by the PTX NCs. Significant increases in intracellular accumulation of 3H-PTX (P-gp substrate) were observed in an MDR cell line (H460/taxR cells) treated with Brij 78 (MHLB=1.11) and Brij 97 (MHLB=0.6). After treatments with Brij 78 and Brij 97, the levels of intracellular ATP were decreased and verapamil induced ATPase activities of P-gp were inhibited in multidrug resistant cells. The responses of the cells to Brij 78 and Brij 97 in ATP depletion studies correlated with the cell viability induced by PTX/Brij NCs and intracellular accumulation of 3H-PTX. Brij 78 and Brij 97 could not alter the levels of P-gp expression detected by western blotting. These findings may provide some insight into the likelihood of further development of more potent P-gp inhibitors for the treatment of MDR in cancer. |
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Authors:
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Jingling Tang; Yongjun Wang; Dun Wang; Yuhua Wang; Zhenghong Xu; Kelly Racette; Feng Liu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-14 |
Journal Detail:
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Title: Biomacromolecules Volume: - ISSN: 1526-4602 ISO Abbreviation: Biomacromolecules Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100892849 Medline TA: Biomacromolecules Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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