External zinc stimulates proliferation of tumor Hep-2 cells by active modulation of key signaling pathways
Abstract
The effect of external zinc supplementation (10 and 35 mikro mol) on cell proliferation and mitogenic signaling of Hep-2 tumor cells was examined during 72 h of treatment. Zinc levels were manipulated by using zinc-free cultivation medium with or without addition of zinc ions.
Proliferation of Hep-2 cells exposed to zinc-free medium decreased in a time-dependent manner and corresponded to decreasing Intracellular zinc content. Hep-2 cells accumulated in G(0)/G(1) phase, showed reduced abundance of AKT and NF-kappa B as well as of anti-apoptotic Bcl-2 and Bcl-XL proteins.
Zinc supplied to Hep-2 cells maintained in the presence of zinc-free medium stimulated their proliferation as well as mitogenic signaling which paralleled increasing intracellular zinc content. In zinc-exposed Hep-2 cells, several changes in various mitogenic signaling pathways were noted such as enhanced expression of p53, AKT and MAP kinases, NF-kappa B and increased DNA binding of AP-1 family.