||Staurosporine, a microbial alkaloid, significantly inhibits protein kinase C from rat brain with IC50 of 2.7 nM. Staurosporine displays strong inhibitory effect against HeLa S3 cells with IC50 of 4 nM.  Staurosporine also inhibits a variety of other protein kinases, including PKA, PKG, phosphorylase kinase, S6 kinase, Myosin light chain kinase (MLCK), CAM PKII, cdc2, v-Src, Lyn, c-Fgr, and Syk with IC50 of 15 nM, 18 nM, 3 nM, 5 nM, 21 nM, 20 nM, 9 nM, 6 nM, 20 nM, 2 nM, and 16 nM, respectively.  Staurosporine (1 μM) induces >90% apoptosis in PC12 cells. Consistently, Staurosporine treatment induces a rapid and prolonged elevation of intracellular free calcium levels [Ca2+]i, accumulation of mitochondrial reactive oxygen species (ROS), and subsequent mitochondrial dysfunction.  The apoptosis of MCF7 cells induced by Staurosporine can be enhanced by the expression of functional caspase-3 via caspase-8 activation and Bid cleavage.  Staurosporine treatment at 1 μM only partially inhibits IL-3-stimulated Bcl2 phosphorylation but completely blocks PKC-mediated Bcl2 phosphorylation.  Staurosporine induces apoptosis of human foreskin fibroblasts AG-1518, depending on the lysosomal cathepsins D mediated cytochrome c release and caspase activation.  In addition to activating the classical mitochondrial apoptosis pathway, Staurosporine triggers a novel intrinsic apoptosis pathway, relying on the activation of caspase-9 in the absence of Apaf-1.