Osmoregulation of Taurine Efflux from Cultured Human Breast Cancer Cells: Comparison with Volume Activated Cl^- Efflux and Regulation by Extracellular ATP

Abstract

The properties and regulation of volume-activated taurine efflux from MDA-MB-231 and MCF-7 cells have been investigated. Volume-activated taurine release from both cell lines was almost completely inhibited by diidosalicylate. DIDS , was more effective at inhibiting swelling-induced taurine release from MCF-7 than from MDA-MB-231 cells. On the basis of comparing taurine, Cl^- and I^- efflux time courses, it appears that volume-activated taurine efflux does not utilize volume-sensitive anion channels in MDA-MB- 231 and MCF-7 cells. Extracellular ATP stimulated volume-activated taurine release from MDA-MB-231 cells but not from MCF-7 cells. The effect of ATP was mimicked by UTP and was dependent upon external calcium and inhibited by suramin. However, suramin inhibited volume-activated taurine efflux from both MDA-MB-231 and MCF-7 cells even in the absence of exogenously added ATP suggesting that it acts directly on the taurine efflux pathway and/or is inhibiting the effect of ATP released from the cells. Volumeactivated taurine efflux from MDA-MB-231 cells was stimulated by ionomycin. In contrast, ionomycin had no effect on taurine release from MCF-7 cells. Adenosine also stimulated volume-activated taurine efflux from MDA-MB-231 cells. The results suggest that purines regulate taurine transport in MDA-MB- 231 cells via more than one type of receptor.

Specificity of the volume-activated amino acid efflux pathway in cultured human breast cancer cells

“…Volume-sensitive taurine release from MCF-7 cells is not increased by the addition of exogenous ATP (Shennan et al 2006). We now show that swelling-induced glycine efflux is also unaffected by ATP (Fig.…”

“…We have previously shown that volume-activated taurine efflux from MDA-MB-231 cells is markedly enhanced by ATP (Shennan et al 2006). In view of this we tested the effect of ATP on swelling-induced AIB, glycine and D-aspartate efflux from MDA-MB-231 cells.…”

“…Human breast cancer cells, in common with other cell types, express mechanisms which facilitate a regulatory volume decrease. For example, cell swelling increases the efflux of K + (Rb + ), Cl -(I -) and taurine from both MDA-MB-231 and MCF-7 cells (Horton et al 1998;Gow et al 2005;Marin et al 2005;Shennan et al 2006;vanTol et al 2007;Roy et al 2008). However, the molecular identities of all the pathways involved in breast cancer cell volume regulation are unknown with the exception of two K + channels, namely KCNQ1 and hERG (vanTol et al 2007;Roy et al 2008).…”

“…Volume-activated taurine efflux from human breast cancer cells is via a pathway sensitive to anion channel blockers such as DIDS and diiodosalicylate but it is evident that the pathway is distinct from Cl -channels (Shennan et al 2006). At present, it is not known if the taurine channel in breast cancer cells is specific for taurine or also allows α-amino acids to pass through.…”

Estrogen regulation and ion dependence of taurine uptake by MCF-7 human breast cancer cells

“…Taurine uptake via TauT could act to maintain the intracellular levels of taurine which subsequently could be used to help MCF-7 cells regulate their volume. In this connection we have evidence that an increase in the cellular hydration state of MCF-7 cells leads to a rapid increase in taurine release from the intracellular compartment via a pathway which is inhibited by DIDS [23]. Therefore, inhibition of taurine uptake by breast cancer cells could compromise cell volume regulation and thus cell survival given that the cellular hydration state is linked to a number of vital processes.…”