Staurosporine cytotoxicity effects

Figure 2. Dose-response neurotropic and cytotoxicity effects of staurosporine on PC 12 cells. Light micrographs of untreated (A) and treated cells (B) for 24 hours with staurosporine (25 nM). (C) Neurotropic and cytotoxicity effects of staurosporine, evaluated 24 hours upon toxin addition.

Staurosporine (36), an indole carbazol alkaloid isolated from Streptomyces staurosporeus was considered the most potent protein kinase inhibitor until the discovery of balanol. Staurosporine is not a selective inhibitor because it also inhibits PKA, PKG and tyrosine kinases at similar concentrations [1], This compound has significant cytotoxic and antiproliferative effects in vitro and several of its related analogues show antitumour activity in animal models. In addition, staurosporine and derivatives have been used to explore the role of PKC in cell functions. For instance, Jordan et al. [95] studied the ability of staurosporine and other PKC inhibitors to affect TNFa and interleukin-la (EL-la)-induced chemokine gene expression and protein production in synovial fibroblasts. In these circumstances, staurosporine enhanced IL-la-induced chemokine mRNA production. A possible explanation for this result is that the mechanisms of gene expression could be negatively regulated by different isoforms of PKC. [95]. Previously it had been observed that staurosporine... 

Staurosporine possesses dual, dose-dependent effects (Rasouly et al., 1992). In the range of 100-500 nM staurosporine inhibited NGF action by reducing trk tyrosine kinase activity and caused cytotoxicity (figure 2). At 10-100 nM, staurosporine induced neurite outgrowth (figure 2) similarly to NGF action, both in PC 12 cells and other neuronal cell cultures. 

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