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Augmentation of transport for cisplatin-glutathione adduct in cisplatin-resistant cancer cells.
Cancer Res. 1995 Oct 01; 55(19):4297-301.CR

Abstract

We studied the outward transport of cisplatin (CDDP)-glutathione (GSH) adduct (DDP-GSH) in CDDP-resistant cancer cells. Incubating the cells in the presence of CDDP resulted in the formation of an adduct with GSH and subsequent transport outside the cells. We used human colonic cancer cells sensitive (HCT8) and resistant (HCT8DDP) to CDDP and human ovarian cancer cells sensitive (A2780) and resistant (A2780DDP) to CDDP as materials. The concentration of intracellular GSH was higher in the resistant cells (118.7 +/- 5.9 nmol/10(6) HCT8DDP versus 19.0 +/- 1.0 nmol/10(6) HCT8 and 24.1 +/- 1.2 nmol/10(6) A2780DDP versus 9.4 +/- 0.5 nmol/10(6) A2780, respectively). The activity of the GSH-synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS) was higher in the CDDP-resistant cells (7.1 +/- 0.2 milliunits/10(6) HCT8DDP versus 2.2 +/- 0.1 milliunits/10(6) HCT8 and 2.9 +/- 0.1 milliunits/10(6) A2780DDP versus 1.4 +/- 0.1 milliunits/10(6) A2780, respectively). Furthermore, immunological levels of gamma-GCS and the expression of gamma-GCS mRNA were higher in these CDDP-resistant cells than those in the control cells, in accordance with the change in the concentration of GSH. DDP-GSH transport increased in the CDDP-resistant colonic cancer cells by 219% (324 +/- 12 fmol/10(6) HCT8DDP cells/min versus 148 +/- 11 fmol/10(6) HCT8 cells/min) and the CDDP-resistant ovarian cancer cells by 126% (127 +/- 7 fmol/10(6) A2780DDP cells/min versus 101 +/- 8 fmol/10(6) A2780 cells/min). DDP-GSH transport was also estimated using inside-out vesicles from these cells. The active transport of DDP-GSH was 243% of HCT8 in HCT8DDP and 121% of A2780 in A2780DDP. These data suggest that the acquisition of CDDP resistance in cancer cells is due partly to the increase in the transport of DDP-GSH outside the cells as well as the increase in the concentration of GSH. Immunological estimation of the membrane proteins against human erythrocyte glutathione S-conjugate-stimulated Mg(2+)-ATPase sera resulted in no apparent cross-reactivity, suggesting that there are several transport systems for DDP-GSH.

Authors+Show Affiliations

Department of Pathological Biochemistry, Nagasaki University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7671239

Citation

Goto, S, et al. "Augmentation of Transport for Cisplatin-glutathione Adduct in Cisplatin-resistant Cancer Cells." Cancer Research, vol. 55, no. 19, 1995, pp. 4297-301.
Goto S, Yoshida K, Morikawa T, et al. Augmentation of transport for cisplatin-glutathione adduct in cisplatin-resistant cancer cells. Cancer Res. 1995;55(19):4297-301.
Goto, S., Yoshida, K., Morikawa, T., Urata, Y., Suzuki, K., & Kondo, T. (1995). Augmentation of transport for cisplatin-glutathione adduct in cisplatin-resistant cancer cells. Cancer Research, 55(19), 4297-301.
Goto S, et al. Augmentation of Transport for Cisplatin-glutathione Adduct in Cisplatin-resistant Cancer Cells. Cancer Res. 1995 Oct 1;55(19):4297-301. PubMed PMID: 7671239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Augmentation of transport for cisplatin-glutathione adduct in cisplatin-resistant cancer cells. AU - Goto,S, AU - Yoshida,K, AU - Morikawa,T, AU - Urata,Y, AU - Suzuki,K, AU - Kondo,T, PY - 1995/10/1/pubmed PY - 1995/10/1/medline PY - 1995/10/1/entrez SP - 4297 EP - 301 JF - Cancer research JO - Cancer Res. VL - 55 IS - 19 N2 - We studied the outward transport of cisplatin (CDDP)-glutathione (GSH) adduct (DDP-GSH) in CDDP-resistant cancer cells. Incubating the cells in the presence of CDDP resulted in the formation of an adduct with GSH and subsequent transport outside the cells. We used human colonic cancer cells sensitive (HCT8) and resistant (HCT8DDP) to CDDP and human ovarian cancer cells sensitive (A2780) and resistant (A2780DDP) to CDDP as materials. The concentration of intracellular GSH was higher in the resistant cells (118.7 +/- 5.9 nmol/10(6) HCT8DDP versus 19.0 +/- 1.0 nmol/10(6) HCT8 and 24.1 +/- 1.2 nmol/10(6) A2780DDP versus 9.4 +/- 0.5 nmol/10(6) A2780, respectively). The activity of the GSH-synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS) was higher in the CDDP-resistant cells (7.1 +/- 0.2 milliunits/10(6) HCT8DDP versus 2.2 +/- 0.1 milliunits/10(6) HCT8 and 2.9 +/- 0.1 milliunits/10(6) A2780DDP versus 1.4 +/- 0.1 milliunits/10(6) A2780, respectively). Furthermore, immunological levels of gamma-GCS and the expression of gamma-GCS mRNA were higher in these CDDP-resistant cells than those in the control cells, in accordance with the change in the concentration of GSH. DDP-GSH transport increased in the CDDP-resistant colonic cancer cells by 219% (324 +/- 12 fmol/10(6) HCT8DDP cells/min versus 148 +/- 11 fmol/10(6) HCT8 cells/min) and the CDDP-resistant ovarian cancer cells by 126% (127 +/- 7 fmol/10(6) A2780DDP cells/min versus 101 +/- 8 fmol/10(6) A2780 cells/min). DDP-GSH transport was also estimated using inside-out vesicles from these cells. The active transport of DDP-GSH was 243% of HCT8 in HCT8DDP and 121% of A2780 in A2780DDP. These data suggest that the acquisition of CDDP resistance in cancer cells is due partly to the increase in the transport of DDP-GSH outside the cells as well as the increase in the concentration of GSH. Immunological estimation of the membrane proteins against human erythrocyte glutathione S-conjugate-stimulated Mg(2+)-ATPase sera resulted in no apparent cross-reactivity, suggesting that there are several transport systems for DDP-GSH. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/7671239/Augmentation_of_transport_for_cisplatin_glutathione_adduct_in_cisplatin_resistant_cancer_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7671239 DB - PRIME DP - Unbound Medicine ER -