Augmentation of cisplatin sensitivity in cisplatin‐resistant human bladder cancer cells by modulating glutathione concentrations and glutathione‐related enzyme activities

Abstract

OBJECTIVES To investigate the roles of glutathione and glutathione‐S‐transferase (GST) in cisplatin‐resistance mechanisms in human bladder cancer, by using glutathione‐depleting or GST‐blocking agents. MATERIALS AND METHODS Cisplatin‐resistant human bladder cancer cell lines were established by continuous exposure of T24 cells to increasing concentrations of cisplatin. Buthionine sulphoximine (BSO), ethacrynic acid and indomethacin were used to deplete glutathione or block GST. Intracellular glutathione content, GST activity and cisplatin cytotoxicity were determined after exposing parental and drug‐resistant cell lines to these agents. RESULTS Intracellular glutathione content and GST activity were significantly decreased, and cisplatin cytotoxicity significantly enhanced, in both parental and resistant cell lines by glutathione‐depleting or GST‐blocking agents. However, the resistance of cisplatin‐resistant cell lines did not fully recover to that of the parental cells with combined BSO and indomethacin. CONCLUSIONS Both increased glutathione content and GST activity are significant in the cisplatin resistance of human bladder tumour cells. Because BSO, ethacrynic acid and indomethacin caused a partial recovery of resistance in the cisplatin‐resistant cell line, further studies are needed to investigate their efficacy for treating patients with metastatic bladder carcinoma resistant to cisplatin.

Synergistic antitumor effect of ginsenoside Rg3 and cisplatin in cisplatin-resistant bladder tumor cell line

“…Bladder cancer cells (HTB5, J82, JON, UMUC14 and T24) were obtained from ATCC (Manassas, VA, USA). T24R2 cisplatin-resistant bladder cancer cells were generated by serial desensitization (6). The cells were maintained in RPMI (T24, T24R2), Dulbecco's modified Eagle's medium (J82, UMUC14) and modified Eagles' medium (HTB5) supplemented with 10% fetal bovine serum (Mediatech, Herndon, VA, USA) and 100 U/ml penicillin/100 mg/l of streptomycin (Invitrogen, Carlsbad, CA, USA).…”

Curcumin and its Analogues (PGV-0 and PGV-1) Enhance Sensitivity of Resistant MCF-7 Cells to Doxorubicin through Inhibition of HER2 and NF-kB Activation

“…However, the use of Dox causes resistance of the cancer cells. Dox induces the expression of P-glycoprotein (Pgp) (Byun et al, 2005) that possibly correlated to the NF-κB activation (Shishodia et al, 2003). Therefore, decreasing the expression and inhibiting of HER2, EGFR, ER, GST, COX-2, NF-κB and Pgp should A) Curcumin ((1E,6E)-1-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-methylphenyl)hepta-1,6-diene-3,5-dione); B) PGV-0…”

Ascorbic Acid (Vitamin C)-Mediated Protection on Mutagenic Potentials of Cisplatin in Mice Bearing Ascites Dalton ’s Lymphoma

“…This detoxification ability plays a role in cellular defenses from environmental and oxidative stress. Moreover, overexpression of specific GSTs can also affect chemoresistance (Hamada et al, 1994;Byun et al, 2005), whereas polymorphisms that decrease GST activity are associated with a high risk of developing cancer (Balendiran et al, 2004). In the present study, cisplatin-mediated decrease in GST activity in liver (Fig.…”