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Rapid stimulation of rhodamine 123 efflux from multidrug-resistant KB cells by progesterone.

Abstract：

:Rhodamine 123 is a mitochondrial dye that is retained for prolonged periods by carcinoma cells. While investigating causes of retention of this dye, we found that 10 microM progesterone caused a rapid stimulation of efflux of rhodamine 123 within 15 min from KB V20C cells, which overexpress the multidrug resistance pump. Progesterone did not stimulate efflux from KB cells that do not overexpress the pump, and verapamil blocked rhodamine 123 efflux in the presence or absence of progesterone, indicating that rhodamine 123 is removed from KB V20C cells by the multidrug resistance pump. Progesterone, however, is unlikely to stimulate rhodamine 123 efflux by simply increasing pump activity for two reasons: (1) progesterone inhibited the efflux of daunomycin from KB V20C cells, so it did not stimulate efflux of all drugs, and (2) progesterone inhibited efflux of rhodamine 123 from L1210/VMDRC cells and had little effect on Adr MCF7 cells; both overexpress the multidrug resistance pump. In the experiments with KB V20C cells, progesterone was the most active steroid tested. At 10 microM, progesterone caused a 70-fold stimulation, desoxycorticosterone, testosterone, promegestone and estradiol about 20-fold, and others had little or no effect. Progesterone may act by a non-genomic mechanism to decrease intracellular binding of rhodamine 123, making the dye accessible to the multidrug resistance pump.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Jancis EM,Chen HX,Carbone R,Hochberg RB,Dannies PS

doi

10.1016/0006-2952(93)90331-p

subject

Has Abstract

pub_date

1993-11-02 00:00:00

pages

1613-9

issue

9

eissn

0006-2952

issn

1873-2968

pii

0006-2952(93)90331-P

journal_volume

46

pub_type

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