Staurosporine is a natural product originally isolated in 1977 from the
bacterium Streptomyces staurosporeus by Omura et al . It was the
first of over 50 alkaloids to be isolated with this type of chemical structure.
The chemical structure of Staurosporine was elucidated by X-ray analysis of a
single crystal and the absolute stereochemical configuration by the same
method in 1994 .
Staurosporine was discovered to have biological
activities ranging from anti-fungal to anti-hypertensive. The interest in these
activities resulted in a large investigative effort in chemistry and biology and
the discovery of the potential for anti-cancer treatment. This led to the
chemical synthesis of Staurosporine itself followed by the synthesis of
compounds that had increasingly diverse chemical structure and their biological
assessment.
Staurosporine is a potent inhibitor of many, many kinases including
protein kinase C (IC50 = 0.7 nM), protein kinase A
(IC50 = 7 nM), and protein kinase G (IC50
= 8.5 nM). Matsumoto, H. and Sasaki, Y. "Staurosporine, a protein kinase C
inhibitor, interferes with proliferation of arterial smooth muscle cells." Biochem.
Biophys. Res. Commun.158: 105-109 (1989). Tamaoki, T., et
al. "Staurosporine, a potent inhibitor of phospholipid/Ca++dependent
protein kinase." Biochem. Biophys. Res. Commun.135: 397-402
(1986).
Staurosporine induces apoptosis in human neuroblastoma cell lines and
chick embryonic neurons. Boix, J., et al. "Characterization of the
cell death process induced by staurosporine in human neuroblastoma cell
lines." Neuropharmacology36: 811-821 (1997). Wiesner, D.A.
and Dawson, G., "Staurosporine induces programmed cell death in embryonic
neurons and activation of the ceramide pathway." J. Neurochem.66:
1418-1425 (1996).
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Induction of Apoptosis by Treatment with Staurosporine
Staurosporine (Streptomyces staurospores) is a relatively
non-selective protein kinase inhibitor, which blocks many kinases to different
degrees. Staurosporine is often used as a general method for inducing apoptosis.
Protocol for Staurosporine-induced Apoptosis:
Add 1 mM (final concentration) staurosporine
(eg, Sigma S6942) to cell suspension (eg, 5 x 105 cells/ml in
tissue culture medium).
Perform a time course to obtain optimum results; a 1-6 hr incubation at
37°C is suggested.
Proceed with assays designed to evaluate induction of apoptosis.
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source: Kabir J, Lobo M, Zachary I. 2002 Staurosporine induces endothelial
cell apoptosis via focal adhesion kinase dephosphorylation and focal adhesion
disassembly independent of focal adhesion kinase proteolysis. J. Biochem.
367: 145-155.
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