|MAXWELL, ELLEN - Institute Of Food Research (IFR)|
|COLQUHOUN, IAN - Institute Of Food Research (IFR)|
|ROLIN, CLAUS - Cp Kelco Us, Inc|
|Chau, Hoa - Rose|
|WALDRON, KEITH - Institute Of Food Research (IFR)|
|MORRIS, VICTOR - Institute Of Food Research (IFR)|
|BELSHAW, NIGEL - Institute Of Food Research (IFR)|
Submitted to: Carbohydrate Polymers
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/23/2015
Publication Date: 7/3/2015
Publication URL: http://handle.nal.usda.gov/10113/61658
Citation: Maxwell, E.G., Colquhoun, I.J., Rolin, C., Chau, H.K., Hotchkiss, A.T., Waldron, K.W., Morris, V.J., Belshaw, N.J. 2015. Rhamnogalacturonan I containing homogalacturonan inhibits colon cancer cell proliferation by decreasing ICAM1 expression. Carbohydrate Polymers. 132:546-553. DOI: 10.1016/j.carbpol.2015.06.082
Interpretive Summary: While pectin is a common ingredient used in jams and other foods, small pectin fragments have anti-cancer activity reported to be due to blocking tumor cell metastasis. However, very little information is available other than pectin binding to a carbohydrate-binding protein that plays a significant role in cancer and other chronic diseases, or how it is absorbed in the gut. We report that the pectin branched region, containing both its backbone and side chains, is responsible for reduction of colon cancer cell growth and proliferation. Furthermore, the pectin branched region reduced expression of a gene involved in colon cancer cellular adhesion. This new information provides a novel molecular mechanism with potential for control and prevention of cancer metastasis in the future.
Technical Abstract: Pectin modified with pH, heat or enzymes, has previously been shown to exhibit anti-cancer activity. However, the structural requirements for bioactive modified pectins have rarely been addressed. In this study several pectin extracts representing different structural components of pectin were assessed for effects against colon cancer cells. Rhamnogalacturonan I (RGI) extracts reduced proliferation of DLD1 and HCT116 colon cancer cells in a dose- and time-dependent manner. RGI reduced ICAM1 gene expression and siRNA-mediated knockdown of ICAM1 expression decreased cell proliferation providing a novel mechanism for the anti-cancer activity of pectin. Structural analysis of bioactive and non-bioactive RGIs showed that a homogalacturonan component is essential for the anti-proliferative activity furthering the understanding of the structural requirements for pectin bioactivity.