A polyphenol mixture from cinnamon targets p38 MAP kinase-regulated signaling pathways to produce G2/M arrest

• Published in: The Journal of nutritional biochemistry 2009-08, Vol.20 (8), p.614-620
• Main Authors: Schoene, Norberta W., Kelly, Meghan A., Polansky, Marilyn M., Anderson, Richard A.
• Format: Article
• Language: English
• Subjects: anticarcinogenic activity; apoptosis; biochemical pathways; Biological and medical sciences; cell cycle; Cell Cycle - drug effects; Cell Size - drug effects; chemoprevention; Cinnamomum verum; Cinnamomum zeylanicum; Cinnamon; Clone Cells; Cyclin B - drug effects; Cyclin B - genetics; Cyclin B1; cyclin-dependent kinase; Feeding. Feeding behavior; Flavonoids - pharmacology; Flow Cytometry - methods; Fundamental and applied biological sciences. Psychology; G2/M; Gene Expression Regulation, Enzymologic; Humans; Jurkat Cells; leukemia; Leukocyte Common Antigens - deficiency; MAP Kinase Signaling System - drug effects; mitogen-activated protein kinase; nutritional intervention; p38 MAPK; p38 Mitogen-Activated Protein Kinases - drug effects; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Phenols - pharmacology; phosphorylation; phytochemicals; plant extracts; Plant Extracts - pharmacology; Polyphenols; spices; supercritical fluid extraction; transcription factors; Tumor Cells, Cultured; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2008.06.006

We recently demonstrated that treatment of three leukemic cell lines with an aqueous extract of cinnamon (CE) for 24 h produced dose-dependent arrests in the G2/M phase of the cell cycle. To accomplish the goal of understanding underlying mechanisms, we selected the cell line most responsive to the CE treatment to study the effects of the extract on signaling molecules regulating cell cycle progression. Cell cycle analyses were conducted on treated versus nontreated cells from 0–6 h. The percentages of cells in G2/M in CE-treated cells increased significantly from 11.0±1.0 to 23.6±1.4 after 6 h, while the percentage for nontreated cells remained unchanged (12.3±0.8). Multiparametric flow cytometric analyses were used to associate activation of p38 mitogen-activated protein kinase (MAPK) with cells arrested in G2/M, the size of these cells, and the presence or absence of cyclin B1. After 4 h, there was a 26% increase in the activated phosphorylated form of p38 MAPK in CE-treated cells compared with the nontreated control cells, with larger cells showing the greater increases. Although the proportion of CE-treated cells in G2/M was higher than controls, this population was shown to be less positive for cyclin B1 than the control G2/M population. Our results demonstrate that CE significantly modulated two signaling proteins, p38 MAPK and cyclin B, that regulate progression through G2/M. Overall, the data provide evidence that CE affects proliferation in a leukemic cell line by disrupting critical phosphorylating/dephosphorylating signaling events that propel cells through the G2/M phase.