Document Detail

Key structure of brij for overcoming multidrug resistance in cancer.
MedLine Citation:
PMID:  23311629     Owner:  NLM     Status:  MEDLINE    
Multidrug resistance (MDR) is a major barrier to the chemotherapy treatment of many cancers. However, some nonionic 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, that is, 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 (CH(2))). Cell viability of cells treated with paclitaxel (PTX) nanocrystals (NCs) formulated with Brij showed positive correlations with MHLB (R(2) = 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 (3)H-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 (3)H-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.
Jingling Tang; Yongjun Wang; Dun Wang; Yuhua Wang; Zhenghong Xu; Kelly Racette; Feng Liu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-24
Journal Detail:
Title:  Biomacromolecules     Volume:  14     ISSN:  1526-4602     ISO Abbreviation:  Biomacromolecules     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-11     Completed Date:  2013-08-01     Revised Date:  2014-02-13    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  United States    
Other Details:
Languages:  eng     Pagination:  424-30     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphatases / antagonists & inhibitors*
Adenosine Triphosphate / metabolism*
Antineoplastic Agents, Phytogenic / pharmacology
Biological Transport / drug effects
Calcium Channel Blockers / pharmacology
Cell Line, Tumor
Cell Survival / drug effects
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Hydrophobic and Hydrophilic Interactions
Lung Neoplasms / drug therapy
P-Glycoprotein / antagonists & inhibitors*
Paclitaxel / pharmacology
Plant Oils / pharmacology*
Polyethylene Glycols / pharmacology*
Surface-Active Agents / pharmacology
Verapamil / pharmacology
Grant Support
5R01CA149387/CA/NCI NIH HHS; R01 CA149387/CA/NCI NIH HHS
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Brij 30; 0/Calcium Channel Blockers; 0/P-Glycoprotein; 0/Plant Oils; 0/Polyethylene Glycols; 0/Surface-Active Agents; 33069-62-4/Paclitaxel; 8L70Q75FXE/Adenosine Triphosphate; 9004-98-2/polyethylene glycol oleyl ether; 9005-00-9/octadecyl polyoxyethylene ether; CJ0O37KU29/Verapamil; EC 3.6.1.-/Adenosine Triphosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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