title: A Novel Cinnamon-Related Natural Product with Pim-1 Inhibitory Activity Inhibits Leukemia and Skin Cancer.
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.
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang 232-916, Republic of Korea.|The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.|WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Joe Eun
authors.initials: JE
authors.lastname: Son
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Hyein
authors.initials: H
authors.lastname: Jeong
authors.affiliation: The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Joon Kim
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Sang Kwon
authors.initials: SK
authors.lastname: Seo
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.|Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang 232-916, Republic of Korea.|The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Lim
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang 232-916, Republic of Korea.|WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Jong Rhan
authors.initials: JR
authors.lastname: Kim
authors.affiliation: The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang 232-916, Republic of Korea.|WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011897:Random Allocation; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D023041:Xenograft Model Antitumor Assays
chemical_list: D002934:Cinnamates; D047428:Protein Kinase Inhibitors; C117045:p-hydroxycinnamaldehyde; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1