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

详细信息    查看全文

• 作者：Danielle Caron ; Pierre E. Savard ; Charles J. Doillon ; Martin Olivier ; Eric Shink ; Jacques G. Lussier ; Robert L. Faure
• 关键词：bpV(phen) ; potassium bisperoxo(1 ; 10-phenanthroline)oxo-vanadate ; PTPs ; protein tyrosine phosphatases ; Cdks ; cyclin-dependent kinases
• 刊名：Cancer Letters
• 出版年：2008
• 出版时间：18 April 2008
• 年：2008
• 卷：262
• 期：2
• 页码：265-275
• 全文大小：848 K

文摘

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.