Thapsigargin, derived from the plant genus Thapsia, is an extremely tight-binding inhibitor of intracellular Ca2+ pumps. It was initially described as a tumor promoting agent which induces rapid Ca2+ release from intracellular stores by inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+-dependent ATPase pump without inositol phosphate formation.The thapsigargin induced depletion of Ca2+ stores causes apoptosis in most cell lines. It has also been shown to cause histamine secretion from rat mast cells, and to stimulate arachidonic acid metabolism in macrophages. Its tumour-promoting function probably results, at least partly, from cytotoxicity, causing a wound response in skin. The tumorogenic activity of thapsigargin might be due to its activation of protein kinase B (Akt) which subsequently stimulates MAP kinase signaling via Src and Raf-1.
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