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Cancer Res. 2015 Jul 1;75(13):2716-2728. doi: 10.1158/0008-5472.CAN-14-3655. Epub 2015 May 6.

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

Kim JE#1,2,3, Son JE#1,4, Jeong H4, Joon Kim D3, Seo SK4, Lee E4,5, Lim TG1,2,3, Kim JR1,2,4, Chen H3, Bode AM3, Lee KW1,2,4, Dong Z3.

Author information

1
Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
2
Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang 232-916, Republic of Korea.
3
The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
4
WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
5
Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea.
#
Contributed equally

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.

PMID:
25948588
PMCID:
PMC4490130
DOI:
10.1158/0008-5472.CAN-14-3655
[Indexed for MEDLINE]
Free PMC Article

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