Glycobiology Advance Access originally published online on May 19, 2007
Glycobiology 2007 17(8):805-819; doi:10.1093/glycob/cwm054
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Pectin induces apoptosis in human prostate cancer cells: correlation of apoptotic function with pectin structure
2 Complex Carbohydrate Research Center
3 Department of Biochemistry and Molecular Biology, The University of Georgia, Athens, GA 30602
4 Medical College of Georgia and VA Medical Center, Augusta, GA 30912
1 To whom correspondence should be addressed; Tel. +1 706 542 4458: Fax: +1 706 542 4412: e-mail: dmohnen{at}ccrc.uga.edu
Received on September 26, 2006; revised on May 9, 2007; accepted on May 11, 2007
Treatment options for androgen-independent prostate cancer cells are limited. Therefore, it is critical to identify agents that induce death of both androgen-responsive and androgen-insensitive cells. Here we demonstrate that a product of plant cell walls, pectin, is capable of inducing apoptosis in androgen-responsive (LNCaP) and androgen-independent (LNCaP C4-2) human prostate cancer cells. Commercially available fractionated pectin powder (FPP) induced apoptosis (approximately 40-fold above non-treated cells) in both cell lines as determined by the Apoptosense assay and activation of caspase-3 and its substrate, poly(ADP-ribose) polymerase. Conversely, citrus pectin (CP) and the pH-modified CP, PectaSol, had little or no apoptotic activity. Glycosyl residue composition and linkage analyses revealed no significant differences among the pectins. Mild base treatment to remove ester linkages destroyed FPP's apoptotic activity and yielded homogalacturonan (HG) oligosaccharides. The treatment of FPP with pectinmethylesterase to remove galacturonosyl carboxymethylesters and/or with endopolygalacturonase to cleave nonmethylesterified HG caused no major reduction in apoptotic activity, implicating the requirement for a base-sensitive linkage other than the carboxymethylester. Heat treatment of CP (HTCP) led to the induction of significant levels of apoptosis comparable to FPP, suggesting a means for generating apoptotic pectic structures. These results indicate that specific structural elements within pectin are responsible for the apoptotic activity, and that this structure can be generated, or enriched for, by heat treatment of CP. These findings provide the foundation for mechanistic studies of pectin apoptotic activity and a basis for the development of pectin-based pharmaceuticals, nutraceuticals, or recommended diet changes aimed at combating prostate cancer occurrence and progression.
Key words: apoptosis / cancer / pectin / prostate / structure