Effect of histone H1 on the cytosolic calcium levels in human breast cancer MCF 7 cells

In human breast cancer MCF 7 cells, the effect of exogenous histone H1 on intracellular calcium ([Ca2+](i)) levels was measured using Fura 2AM. The dose and time dependent assessment revealed significant cell killing effect of histone HI on MCF 7 cells. Historic HI induced a sustained concentration dependent increase in [Ca2+](i) levels in the presence of calcium in the medium, but the increase was reduced in the absence of extra cellular calcium. The effect of histone HI on, intracellular calcium flux measured using Ca-45 radiolabel revealed significant inhibition of calcium uptake in endoplasmic reticulum, whereas the rate of uptake was unaltered in the mitochondria. The activities of phospholipase A(2) showed a significant transient increase at 1 minute which by the end of 5 minutes decreased, whereas the activities of phospholipase C which showed a transient increase at the end of 1 minute, was maintained at basal levels in histone H1 treated cells compared to control cells. These findings suggest that histone HI increases [Ca2+](i) in MCF 7 cells by stimulating both extra cellular calcium influx and intracellular calcium release at higher concentrations exhibiting cytotoxic effect. (c) 2005 Elsevier Inc. All rights reserved.