Effect of buthionine sulfoximine on PtII and PtIV drug accumulation and the formation of glutathione conjugates in human ovarian-carcinoma cell lines - PubMed (original) (raw)
. 1993 Nov 11;55(5):848-56.
doi: 10.1002/ijc.2910550526.
Affiliations
- PMID: 8244583
- DOI: 10.1002/ijc.2910550526
Effect of buthionine sulfoximine on PtII and PtIV drug accumulation and the formation of glutathione conjugates in human ovarian-carcinoma cell lines
P Mistry et al. Int J Cancer. 1993.
Abstract
Glutathione (GSH) has often been implicated in the mechanism of resistance to platinum anti-cancer drugs. It has been suggested that GSH may reduce the cytotoxicity of these drugs by forming inactive conjugates and by enhancing the repair of DNA-platinum crosslinks. In the present study we have examined the effect of D,L-buthionine-S,R-sulfoximine (BSO) pretreatment on the accumulation of platinum in a sensitive (CHI) and 2 relatively resistant (SKOV-3, HX/62) human ovarian-carcinoma cell lines following exposure to PtII- (cisplatin, carboplatin) and PtIV-drugs (tetraplatin). The metabolism of cisplatin and tetraplatin (particularly the extent of platinum-GSH conjugate formation) in the presence and absence of BSO pre-treatment was also examined in these cell lines. BSO pre-treatment reduced the accumulation of PtII but not that of PtIV drugs in the relatively resistant SKOV-3 and HX/62 cell lines. It had no effect on the accumulation of either class of drugs in the sensitive CHI cells. Metabolism studies with cisplatin showed that the SKOV-3 and HX/62 cells, which contained 2- to 3-fold higher levels of GSH, were able to inactivate a greater proportion of cellular cisplatin, by the formation of platinum-GSH conjugates, than the CHI cells. A significant inhibition in formation of these conjugates, by BSO-induced depletion of cellular GSH (over 80%), did not, however, increase cisplatin concentration in the resistant cells. In contrast, a small increase in cisplatin concentration was observed in the sensitive cells following BSO pre-treatment. Comparison of cisplatin and tetraplatin metabolism in the SKOV-3 cells indicated that a greater proportion of the latter drug was inactivated by formation of GSH conjugates. BSO-induced depletion of cellular GSH in this cell line significantly reduced the formation of such conjugates from both drugs. However, concomitant increases in intracellular levels of reactive species were observed only after tetraplatin exposure. Our data suggest that the greater potentiation of PtIV- compared with PtII-drug cytotoxicity in the relatively resistant cell lines following 24 hr BSO pre-treatment may be caused by a differential effect of BSO on the metabolism and cellular distribution of these drugs. A BSO-induced reduction in PtII- but not PtIV-drug accumulation in these cells may also partially contribute to the differential potentiation of cytotoxicity of these drugs.
Similar articles
- The relationships between glutathione, glutathione-S-transferase and cytotoxicity of platinum drugs and melphalan in eight human ovarian carcinoma cell lines.
Mistry P, Kelland LR, Abel G, Sidhar S, Harrap KR. Mistry P, et al. Br J Cancer. 1991 Aug;64(2):215-20. doi: 10.1038/bjc.1991.279. Br J Cancer. 1991. PMID: 1892748 Free PMC article. - Relationship of cellular glutathione to the cytotoxicity and resistance of seven platinum compounds.
Meijer C, Mulder NH, Timmer-Bosscha H, Sluiter WJ, Meersma GJ, de Vries EG. Meijer C, et al. Cancer Res. 1992 Dec 15;52(24):6885-9. Cancer Res. 1992. PMID: 1458477 - Buthionine sulfoximine and chemoresistance in cancer treatments: a systematic review with meta-analysis of preclinical studies.
Dos Reis Oliveira C, Pereira JC, Barros Ibiapina A, Roseno Martins IR, de Castro E Sousa JM, Ferreira PMP, Carneiro da Silva FC. Dos Reis Oliveira C, et al. J Toxicol Environ Health B Crit Rev. 2023 Nov 17;26(8):417-441. doi: 10.1080/10937404.2023.2246876. Epub 2023 Aug 22. J Toxicol Environ Health B Crit Rev. 2023. PMID: 37606035 Review. - Resistance to alkylating agents and cisplatin: insights from ovarian carcinoma model systems.
Perez RP, Hamilton TC, Ozols RF. Perez RP, et al. Pharmacol Ther. 1990;48(1):19-27. doi: 10.1016/0163-7258(90)90015-t. Pharmacol Ther. 1990. PMID: 2274575 Review.
Cited by
- Oxaliplatin: pharmacokinetics and chronopharmacological aspects.
Lévi F, Metzger G, Massari C, Milano G. Lévi F, et al. Clin Pharmacokinet. 2000 Jan;38(1):1-21. doi: 10.2165/00003088-200038010-00001. Clin Pharmacokinet. 2000. PMID: 10668856 Review. - Cytotoxicity of antitumor platinum complexes with L-buthionine-(R,S)-sulfoximine and/or etanidazole in human carcinoma cell lines sensitive and resistant to cisplatin.
Brooks SE, Korbut TT, Dupuis NP, Holden SA, Teicher BA. Brooks SE, et al. Cancer Chemother Pharmacol. 1995;36(5):431-8. doi: 10.1007/BF00686193. Cancer Chemother Pharmacol. 1995. PMID: 7634385 - NMR studies of the relationship between the changes of membrane lipids and the cisplatin-resistance of A549/DDP cells.
Huang Z, Tong Y, Wang J, Huang Y. Huang Z, et al. Cancer Cell Int. 2003 Apr 8;3(1):5. doi: 10.1186/1475-2867-3-5. Cancer Cell Int. 2003. PMID: 12718757 Free PMC article. - Cross-resistance and collateral sensitivity to natural product drugs in cisplatin-sensitive and -resistant rat lymphoma and human ovarian carcinoma cells.
Parekh H, Simpkins H. Parekh H, et al. Cancer Chemother Pharmacol. 1996;37(5):457-62. doi: 10.1007/s002800050412. Cancer Chemother Pharmacol. 1996. PMID: 8599869 - Gamma-glutamyl transpeptidase accelerates tumor growth and increases the resistance of tumors to cisplatin in vivo.
Hanigan MH, Gallagher BC, Townsend DM, Gabarra V. Hanigan MH, et al. Carcinogenesis. 1999 Apr;20(4):553-9. doi: 10.1093/carcin/20.4.553. Carcinogenesis. 1999. PMID: 10223181 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical