Protein tyrosine phosphatase inhibition induces anti-tumor activity: evidence of Cdk2/p27 kip1 and Cdk2/SHP-1 complex formation in human ovarian cancer cells

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(kip1), 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.