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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #206114
Title: A polyphenol mixture from cinnamon targets p38 MAP kinase-regulated signaling pathways to produce G2/M arrest

Author
item Schoene, Norberta
item Kelly, Meghan
item Polansky, Marilyn
item Anderson, Richard

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/9/2008
Publication Date: 10/3/2008
Citation: Schoene, N.W., Kelly, M.A., Polansky, M.M., Anderson, R.A. 2008. A polyphenol mixture from cinnamon targets p38 MAP kinase-regulated signaling pathways to produce G2/M arrest. Journal of Nutritional Biochemistry. 20(8):614-620.

Interpretive Summary: Our diets contain many polyphenolic compounds that have been proposed to have a multitude of beneficial effects on health. Little is known about how these compounds produce these effects. Recently, our laboratory has focused on understanding the health-promoting properties of polyphenolic compounds found in cinnamon. In this report we demonstrated that a water extract of this spice quickly stopped the growth of tumor cell lines grown in culture. Our experiments provided evidence that the cinnamon extract specifically targets two proteins in the cell that are critical regulators of cell growth and cell division. Initially, a protein kinase is activated by the cinnamon extract which then promotes attachment of a phosphate group to another protein complex. This latter complex is inhibited by this action and can no longer induce cellular division. Our results expand on information about critical roles for cinnamon polyphenols in modulating cellular signals via changes in protein phosphorylation. This information provides insights into the mechanisms of actions of the polyphenols in cinnamon that will be of use to nutrition researchers, dietitians, and health care providers.

Technical Abstract: 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 (CE =0.1mg/mL) versus non-treated 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 non-treated cells remained unchanged (12.3 +/- 0.8). Multiparametric flow cytometric analyses were used to associate activation of p38 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 to the non-treated control cells, with larger cells showing the greater increase. 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 tumor cell proliferation by disrupting critical phosphorylating/dephosphorylating signaling events that propel cells through the G2/M phase.