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Abstract Title:

A Novel Cinnamon-Related Natural Product with Pim-1 Inhibitory Activity Inhibits Leukemia and Skin Cancer.

Abstract Source:

Cancer Res. 2015 May 6. Epub 2015 May 6. PMID: 25948588

Abstract Author(s):

Jong-Eun Kim, Joe Eun Son, Hyein Jeong, Dong Joon Kim, Sang Gwon Seo, Eunjung Lee, Tae Gyu Lim, Jong Rhan Kim, Yengo Raymond Kimbung, Hanyong Chen, Ann M Bode, Ki Won Lee, Zigang Dong

Article Affiliation:

Jong-Eun Kim

Abstract:

The Pim-1 kinase regulates cell survival, proliferation, and differentiation and is overexpressed frequently in many malignancies, including leukemia and skin cancer. In this study, we used kinase profiling analysis to demonstrate that 2'-hydroxycinnamicaldehyde (2'-HCA), a compound found in cinnamon, specifically inhibits Pim-1 activity. Cocrystallography studies determined the hydrogen bonding pattern between 2'-HCA and Pim-1. Notably, 2'-HCA binding altered the apo kinase structure in a manner that shielded the ligand from solvent, thereby acting as a gatekeeper loop. Biologically, 2'-HCA inhibited the growth of human erythroleukemia or squamous epidermoid carcinoma cells by inducing apoptosis. The compound was also effective as a chemopreventive agent against EGF-mediated neoplastic transformation. Finally, 2'-HCA potently suppressed the growth of mouse xenografts representing human leukemia or skin cancer. Overall, our results offered preclinical proof of concept for 2'-HCA as a potent anticancer principle arising from direct targeting of the Pim-1 kinase. Cancer Res; 75(13); 1-13.©2015 AACR.

Study Type : Animal Study

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Sayer Ji
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