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Modulation of doxorubicin cytotoxicity by ethacrynic acid

โœ Scribed by Sanjay Awasthi; Sharad S. Singhal; Nong-gao He; Meena Chaubey; Piotr Zimniak; Sanjay K. Srivastava; Shivendra V. Singh; Yogesh C. Awasthi

Publisher
John Wiley and Sons
Year
1996
Tongue
French
Weight
827 KB
Volume
68
Category
Article
ISSN
0020-7136

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โœฆ Synopsis

Energy-dependent membrane efflux pumps have been implicated in mediating resistance to doxorubicin (DOX). Membranetransport mechanisms distinct from P-glycoprotein, capable of transporting DOX and glutathione conjugates have been yeported in human cells. Since glutathione-conjugate-forming compounds may be candidates for modulating the cytotoxicity of certain anti-neoplastic agents transported by such transport mechanism, the present studies were performed (i) to determine whether ethacrynic acid, a glutathione-conjugate-forming diuretic, can increase DOX cytotoxicity, and (ii) to study the kinetics of DOX transport and its inhibition by the glutathione conjugate of ethacrynic acid EA-SG) in the H69 human small-Our results indicate that more than one DOX transport mechanism may exist in these cell lines, and that glutathione conjugates may be useful for modulating the cytotoxic effects of DOX.

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