Bioactive Carbohydrates:

A growing number of plant carbohydrates are claimed to show a range of bioactive properties including wound healing, anti-viral effects and anti-cancer activity.

The role of dietary carbohydrates in cancer progression and metastasis is an emerging field of clinical importance (1). Modified pectin polysaccharides, an important constituent of the cell walls of fruits and vegetables, have been shown to play critical therapeutic roles against cancers (1-3) and in immuno-modulation (4).

The suggested hypothesis (1) for the role of modified pectin is that the product contains structural elements that can bind to and inhibit the function of the mammalian lectin galectin-3 (Gal3) which is considered as a diagnostic marker and a target protein for cancer treatment (5).

Pectin is the most complex polysaccharide produced by plants. By breaking down the pectin structure into its components it has been possible to identify a fragment, a pectin galactan, which binds specifically to Gal3 (6). Using this approach we have identified the bioactive component of pectin (6). Our results are consistent with the proposed molecular model (1) for the anti-cancer action of modified pectin.                    

AFM provides a tool for studying binding between different molecules. By attaching one of the molecules to the cantilever-tip assembly and the other to a suitable substrate it is possible to ‘fish’ for the molecule on the substrate. When the molecules attach to each other a finite force is required to pull them apart. Such specific binding can be used to identify bioactive carbohydrates involved in carbohydrate-lectin binding or to confirm models for bioactivity.

As well as studying interactions between individual molecules it is also possible to use a similar approach to map carbohydrate–protein interactions at the cellular level. This approach can be used to produce an ‘adhesion map’ showing the location of receptors on the cell surface.

Background:

1. Nangia-Makker P, Conklin J, Hogan V & Raz A. Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents. Trends Mol. Medicine 8, 187-192 (2002)

2. Kidd P. A new approach to metastasis cancer prevention: modified citrus pectin (MCP), a unique pectin that blocks cell surface lectins. Altern. Med. Rev. 1, 4-10 (1996)

3. Olano-Martin E, Rimbach GH, Gibson GR & Rastall RA. Pectin and pectic-oligosaccharides induce apoptosis in in vivo human colonic adenocarcinoma cells. Anticancer Research 23, 341-346 (2003)

4. Wong CK, Leung KN & Fung KP. Immunomodulatory and anti-tumor polysaccharides from medicanal plants. J. Int. Med. Res. 22, 299-312 (1994)

5. Takenaka Y, Fukamori T & Raz A. Galectin-3 and metastasis. Glycoconj. J. 19, 543-549 (2004)

6. Ridley BL, O’Neil MA & Mohnen D. Pectins: structure, biosynthesis, and oligogalacturonide-related signalling. Phytochemistry 57, 929-967 (2001)

Further Reading:

7. Gunning AP, Bongaerts RJM & Morris VJ. Recognition of galactan components of pectin by galectin-3. FASEB J. first published on October 2, 2008 (doi:10.1096/fj.08-106617)

8. Gunning, A.P., Chambers, S., Pin, C., Man, A.L., Morris, V.J. and Nicoletti, C. Mapping specific adhesive interactions on living intestinal epithelial cells with atomic force microscopy. FASEB J. 22, 2331-2339 (2008)