ISSN:
1573-0778
Keywords:
anticancer prostaglandins
;
cisplatin
;
drug resistance
;
glutathione
;
GS-X pump
;
MRP
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
,
Process Engineering, Biotechnology, Nutrition Technology
Notes:
Abstract We provide evidence that the expression of the humanMRP/GS-X pump encoded by theMRP (multidrug resistance associated protein) gene is induced by cisplatin in human leukemia HL-60/R-CP (cisplatin-resistant) cells and modulates cell growth inhibition by Δ7-prostaglandin A1 (PGA1) methyl ester. TheMRP mRNA level in HL-60/R-CP cells increased remarkably after a 24-h incubation with 20 μM cisplatin; interestingly, however, no amplification of theMRP gene was detected. In cisplatin-sensitive HL-60 cells, which express theMRP/GS-X pump at low levels, c-myc expression was substantially supressed by Δ7-PGA1 methyl ester and the cell cycle was arrested in G1 phase. By contrast, in HL-60/R-CP cells overexpressing theMRP/GS-X pump, c-myc expression and cell proliferation were much less affected by Δ7-PGA1 methyl ester. This suggests that induction of theMRP/GS-X pump may confer on cancer cells resistance to anticancer prostaglandins and that the resistance mechanism may involve the increased efflux of PG-glutathione conjugates, as active intermediates, from the cells via theMRP/GS-X pump.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00744216
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