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  • Title: Cytotoxicity of vacuolar H(+)-ATPase inhibitors to UMR-106 rat osteoblasts: an effect on iron uptake into cells?
    Author: Hall TJ.
    Journal: Cell Biol Int; 1994 Mar; 18(3):189-93. PubMed ID: 8019493.
    Abstract:
    Treatment of rat osteoblastic UMR-106 cells with bafilomycin A1 rhamnoside or concanamycin A, which are potent and specific inhibitors of the vacuolar H(+)-ATPase (V-ATPase), caused a rapid rounding up of the cells (within 6 hr), inhibition of cell growth (IC50 = 3.3 nM and 0.5 nM, respectively, at 24 hr) and cell death at 54 hr. Since proliferating cells have an absolute requirement for iron and the V-ATPase plays a crucial role in iron uptake into cells via the transferrin cycle, the effect of the iron chelator, desferal, was tested on UMR-106 cells. A time-dependent cell rounding, suppression of cell growth followed by cell death very similar to that observed with the V-ATPase inhibitors was seen. Therefore, the in vitro and in vivo toxicity of V-ATPase inhibitors may be due, at least in part, to their preventing iron uptake into cells.
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