Intracellular GSH Alterations and Its Relationship to Level of Resistance following Exposure to Cisplatin in Cancer Cells

Document Type: Research article

Authors

1 Biopharmaceutics and Pharmacokinetics Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

2 Department of Toxicology & pharmacology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Toxicology and Pharmacology Department, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

4 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Department of Toxicology, SBMU Pharmacy School, Tehran, Iran.

6 SBMU Pharmaceutical Sciences Research Center, P.O.Box 14155-3817, Tehran, Iran.

Abstract

One of the major complications in cancer chemotherapy is the development of resistance, and cisplatin, as one of the important medicines in treatment regimens of different cancers is not excluded. One of the most described cellular defense mechanisms involved in resistance is glutathione (GSH) and in this study, the effects of cisplatin on the total intracellular GSH level (GSHi) in some sensitive and resistant variants of human cell lines (hepatocarcinoma HepG2, Skin A375, cisplatin sensitive glioblastoma U373MG and cisplatin resistant glioblastoma U373MGCP, cisplatin sensitive ovary A2780S and cisplatin resistant A2780CP cells) was studied. MTT assay was used to measure cytotoxicity of cisplatin (33.3 µM for 1 hour). GSHi (per million cells) was evaluated using a photometrical assay up to 90 minutes following cisplatin exposure. Our results indicate that there are significant differences between GSHi content of A2780CP and U373MGCP cells with other cell lines. Moreover, IC50 of cisplatin in different cells seems to have a relation with mean of GSH level in 90 minutes (GSH (mean)90).
As a conclusion, it seems that the acquired resistance to cisplatin in different cell lines is more related with the diverse patterns of GSHi variations following cisplatin than its original level, and/or its cellular increase or decrease. It is also suggested that GSH (mean)90 may be used as a factor for the prediction of cellular resistance to cisplatin.

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