Journal
CANCER LETTERS
Volume 262, Issue 2, Pages 265-275Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2007.12.012
Keywords
bpV(phen); potassium bisperoxo(1,10-phenanthroline)oxo-vanadate; PTPs; protein tyrosine phosphatases; Cdks; cyclin-dependent kinases
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The protein tyrosine phosphatase (PTP) superfamily of enzymes functions with protein tyrosine kinases to regulate a broad spectrum of fundamental physiological processes. Addition of the PTP inhibitor potassium bisperoxo(1,10-phenanthroline)oxo-vanadate(V) [bpV(phen)] to the culture medium of human ovarian cancer cells (OVCAR-3) resulted in a dose-dependent decrease in the formation of tumors in a 3-D culture system. An evaluation of the potency of bpV(phen) in vivo confirmed the anti-tumor activity. Further study of the mechanism of action revealed a 40% decrease in Cdk2 kinase activity, an elevated level of Cdk2/p27(kipl), and the appearance of Cdk2/SHP-1 complexes. Therefore, a cytostatic dose of a PTP inhibitor increases the intracellular levels of Cdk2/p27(kip) and Cdk2/SHP-1 complexes, which indicate the presence of additional mechanisms underlying the anti-tumor activity. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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