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    Membrane model as key tool in the study of glutathione-s-transferase mediated anticancer drug resistance

    Year: 2022

    Journal: Biomed. Pharmacother., Volume 145, JAN

    Authors: Materon, Elsa M.; Shimizu, Flavio M.; dos Santos, Kevin Figueiredo; Nascimento, Gustavo F.; Geraldo, Vananelia P. N.; Oliveira Jr, Osvaldo N.; Faria, Ronaldo C.

    Organizations: Sao Paulo Research Foundation (FAPESP) [2012/15543-7, 2016/00991-5, 2017/24053-7, 2018/22214-6]; Brazilian National Council for Scientific and Technological Development (CNPq), Ministry of Science, Technology and Inovation (MCTI-SisNano, Brazil)

    Keywords: Membrane model; Langmuir monolayer; Cisplatin; Doxorubicin; Detoxification enzyme; Glutathione-s-transferase

    Glutathione-s-transferase is believed to be involved in the resistance to chemotherapeutic drugs, which depends on the interaction with the cell membranes. In this study, we employed Langmuir monolayers of a mixture of phospholipids and cholesterol (MIX) as models for tumor cell membranes and investigated their interaction with the anticancer drugs cisplatin (CDDP) and doxorubicin (DOX). We found that both DOX and CDDP expand and affect the elasticity of MIX monolayers, but these effects are hindered when glutathione-s-transferase (GST) and its cofactor glutathione (GSH) are incorporated. Changes are induced by DOX or CDDP on the polarizationmodulated infrared reflection absorption spectroscopy (PM-IRRAS) data for MIX/GST/GSH monolayers, thus denoting some degree of interaction that is not sufficient to alter the monolayer mechanical properties. Overall, the results presented here give support to the hypothesis of the inactivation of DOX and CDDP by GST and point to possible directions to detect and fight drug resistance.
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