Review
Pectin – An emerging new bioactive food polysaccharide

https://doi.org/10.1016/j.tifs.2011.11.002Get rights and content

Pectin is a constituent of the cell walls of fruits and vegetables, and provides an important source of dietary fibre, as well as being a functional ingredient in processed foods. In addition to the health benefits associated with dietary fibre, new health claims are emerging, particularly with regard to the bioactive roles for modified pectin as an anti-cancer agent. These suggest that the modification creates molecular fragments, some of which may bind to and inhibit the various actions of the pro-metastatic protein galectin-3. The evidence for such a mechanism and the nature of the bioactive fragments will be discussed.

Highlights

► Modified pectin is claimed to have anti-cancer properties. ► Modified pectin is considered to act by inhibiting galectin-3. ► Mechanistic aspects of the role of galectin-3 are discussed. ► Mechanisms for uptake and distribution of modified pectin are discussed.

Introduction

Pectin, a complex structural polysaccharide contained in the cell walls of terrestrial plants, is best known for its use as a gelling and thickening agent or as a source of stabilisers for acidic milk drinks. Pectin, as a constituent of fruit and vegetables, is also a natural component of the human diet, where it contributes to soluble fibre. Although not digested by the upper gastrointestinal tract, there is evidence that soluble fibre is beneficial to health.

Recently, great progress has been made in elucidating structure/function relationships of pectin at a molecular level, and this is leading to the design of pectins with specific functionalities. As well as its importance in the food industry, pectin has potential uses in many other fields. Recently there has been interest in the potential role of pectin in the prevention and reduction of carcinogenesis. New and exciting research is now being carried out into the effects of what is ambiguously called ‘modified pectin’ (MP), pectin that has been broken down into smaller fragments that, in theory, can be absorbed by the body. Mechanisms are unclear; however, evidence suggests that small molecular weight pectin fragments, rich in galactans, can bind to the carbohydrate recognition domain (CRD) on the pro-metastatic protein galectin-3 (GAL3). This binding may block GAL3’s interactions with other proteins and peptides, inhibiting its ability to promote cell adhesion and migration, and to prevent apoptosis. This raises the possibility that MP may be utilised in a potentially safe, non-toxic approach for preventing or reducing carcinogenesis.

A number of patents for producing bioactive MP have been successfully granted; however it is still hard to relate a distinct molecular structure to specific health-related activities. Assorted extraction methods, sources of plants, varying fragmentation techniques, as well as the structural complexity of pectin itself, makes the characterisation of ‘modified pectin’ difficult. The specific structural characteristics responsible for binding to GAL3, as well as the underlying mechanisms behind the anti-metastatic activity need to be ascertained. How MP is absorbed by the body is also unknown; however recent research into the uptake of β-glucans may shed some light on this mystery. This review looks to highlight the latest research into MP, its proposed role as a GAL3 inhibitor and the associated structure/function relationships.

Section snippets

Pectin – a complex polysaccharide

Pectin extracts from cell walls, far from being just one molecule, are a family of polysaccharides with common features (Ridley, O’Neill, & Mohnen, 2001). The most familiar and predominant member is homogalacturonan (HG), known as the ‘smooth region’ of pectin, composed predominantly of a homopolymer of partially methyl-esterified (1-4)-linked α-d-galacturonic acid (GalA). A second well-characterised component constitutes the ‘hairy’ region of pectin or rhamnogalacturonan I (RGI) regions. These

Modified pectin

There is growing evidence linking modified forms of pectic polysaccharides with anti-cancer activity. A proposed explanation for such effects is that these modified polysaccharides contain structural elements that can bind to and inhibit galectin-3 (GAL3), a multifaceted and pro-metastatic protein whose expression is up-regulated in many cancers. MP is commonly produced from commercial pectin as follows: the process involves effectively de-polymerisation using an enzymatic modification, or an

Conclusions

Although there is evidence from numerous studies suggesting that MP inhibits various steps in metastasis by interacting with GAL3, the details of the underlying mechanisms are still largely unknown. Understanding the mechanisms involved is complicated by the structural complexity of pectin and its components, the nature of the plant source and the extraction methods, and the varying fragmentation techniques used to create MP. Therefore, the term ‘modified pectin’ is not well defined, and

Acknowledgements

This work was funded by the Biotechnology and Biological Sciences Research Council through a CASE studentship and the International Pectin Producers Association (IPPA). Additionally we thank Dr Han-Ulrich Endress, Secretary General of the IPPA, for critical reading of the manuscript.

References (57)

  • G.C. Chan et al.

    The effects of beta-glucan on human immune and cancer cells

    Journal of Hematology & Oncology

    (2009)
  • F.E. Cotter et al.

    Clinical caspase activation in CLL by GCS-100, a novel carbohydrate, in a phase 2 study

    Annals of Oncology

    (2008)
  • V.M. Delgado et al.

    Modulation of endothelial cell migration and angiogenesis: a novel function for the "tandem-repeat" lectin galectin-8

    FASEB Journal

    (2011)
  • J.V. Diaz et al.

    Nonenzymatic degradation of citrus pectin and pectate during prolonged heating: effects of pH, temperature, and degree of methyl esterification

    Journal of Agricultural and Food Chemistry

    (2007)
  • I. Eliaz et al.

    The effect of modified citrus pectin on urinary excretion of toxic elements

    Phytotherapy Research

    (2006)
  • Y. Fan et al.

    The inhibitory effect of ginseng pectin on L-929 cell migration

    Archives of Pharmacal Research

    (2010)
  • H. Forsman et al.

    Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis

    Arthritis & Rheumatism

    (2011)
  • G.V. Glinsky et al.

    Inhibition of colony formation in agarose of metastatic human breast carcinoma and melanoma cells by synthetic glycoamine analogs

    Clinical & Experimental Metastasis

    (1996)
  • T.E. Gronhaug et al.

    Beta-D-(1→4)-galactan-containing side chains in RG-I regions of pectic polysaccharides from Biophytum petersianum Klotzsch. contribute to expression of immunomodulating activity against intestinal Peyer’s patch cells and macrophages

    Phytochemistry

    (2011)
  • J.J. Grous et al.

    GCS-100, a galectin-3 antagonist, in refractory solid tumors: a phase I study

    Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I.

    (2006)
  • B.W. Guess et al.

    Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study

    Prostate Cancer and Prostatic Diseases

    (2003)
  • A.P. Gunning et al.

    Recognition of galactan components of pectin by galectin-3

    FASEB Journal

    (2009)
  • A. Hayashi et al.

    Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c mice

    Alternative Medicine Review

    (2000)
  • W. He et al.

    Selective drug delivery to the colon using pectin-coated pellets

    PDA Journal of Pharmaceutical Science and Technology

    (2008)
  • F. Hong et al.

    Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models

    Journal of Immunology

    (2004)
  • T.T. Htwe et al.

    Differential expression of galectin-3 in advancing thyroid cancer cells: a clue toward understanding tumour progression and metastasis

    Singapore Medical Journal

    (2010)
  • H. Idikio

    Galectin-3 expression in human breast carcinoma: correlation with cancer histologic grade

    International Journal of Oncology

    (1998)
  • C.L. Jackson et al.

    Pectin induces apoptosis in human prostate cancer cells: correlation of apoptotic function with pectin structure

    Glycobiology

    (2007)
  • Cited by (345)

    View all citing articles on Scopus
    View full text