Induction of MRP/GS-X pump and cellular resistance to anticancer prostaglandins.

Abstract:

:We provide evidence that the expression of the human MRP/GS-X pump encoded by the MRP (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 delta(7)-prostaglandin A1 (PGA1) methyl ester. The MRP mRNA level in HL-60/R-CP cells increased remarkably after a 24-h incubation with 20 microM cisplatin; interestingly, however, no amplification of the MRP gene was detected. In cisplatin-sensitive HL-60 cells, which express the MRP/GS-X pump at low levels, c-myc expression was substantially suppressed by delta(7)-PGA1 methyl ester and the cell cycle was arrested in G1 phase. By contrast, in HL-60/R-CP cells overexpressing the MRP/GS-X pump, c-myc expression and cell proliferation were much less affected by delta(7)-PGA1 methyl ester. This suggests that induction of the MRP/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 the MRP/GS-X pump.

journal_name

Cytotechnology

journal_title

Cytotechnology

authors

Akimaru K,Kuo MT,Furuta K,Suzuki M,Noyori R,Ishikawa T

doi

10.1007/BF00744216

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

221-7

issue

3

eissn

0920-9069

issn

1573-0778

journal_volume

19

pub_type

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