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• W2956140456 abstract "Background: Glutathione (GSH), which is the predominant low molecular weight intracellular thiol in mammals, has multiple functions, such as those of protecting against oxidative stress and detoxifying endogenous and exogenous electrophiles. High GSH levels, which have been observed in various types of tumors, have been thought to contribute to the resistance of neoplastic cells to apoptotic stimuli triggered by pro-oxidant therapy. Although L-(S,R)-Buthionine Sulfoximine (BSO), a selective irreversible inhibitor of glutamate cysteine ligase, depletes GSH in vitro and in in vivo and sensitizes tumor cells to radiation and some cancer chemotherapeutics, its toxicity and short in vivo half-life have limited its application to combination anticancer therapies. Objective: To demonstrate that a folate-targeted PEGylated BSO conjugate can sensitize cancer cells to a Reactive Oxygen Species (ROS)-generating anticancer agent by depleting GSH. Methods: A novel folate-targeted PEGylated-BSO conjugate was synthesized and tested in combination with gemcitabine in human cell lines that over-express (HeLa) or do not express (A549) the folate receptor. Results: The prepared folate-PEG-GFLG-BSO conjugate proved to be efficacious in reducing GSH levels and, when used in combination with the pro-oxidant drug gemcitabine, it enhanced drug activity in the cell line overexpressing the folate receptor. Conclusion: The folate-PEG-GFLG-BSO conjugate studied was found to be effective in sensitizing folatereceptor positive cancer cells to the ROS-generating drug gemcitabine." @default.
• W2956140456 created "2019-07-12" @default.
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• W2956140456 date "2019-12-02" @default.
• W2956140456 modified "2023-09-25" @default.
• W2956140456 title "Overcoming Cancer Cell Drug Resistance by a Folic Acid Targeted Polymeric Conjugate of Buthionine Sulfoximine" @default.
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• W2956140456 doi "https://doi.org/10.2174/1871520619666190626114641" @default.
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