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

Abstract

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.

Plant Cell Wall Polymers: Function, Structure and Biological Activity of Their Derivatives

“…The extracted pectins of citrus peel and apples are used as a gelling and stabilizing agent in food and cosmetic industries. Pectins within the fruits and vegetables are part of the daily dietary fiber and have multiple positive effects on human health including lowering cholesterol, serum glucose levels, decrease occurrence of diabetes and cancer [17][18][19]. This points the relevance of pectins in diverse emerging fields of study, even in human health.…”

Plant Pectin: A Potential Source for Cancer Suppression

“…Jackson et al (2007) have shown that commercially available plant pectin is effectively capable to induce apoptosis in androgen responsive LNCap and androgen independent LNcaP-C4-2 prostate cancer cells compared with CP, pH modified CP or pectaSol suggesting that specific structural elements within pectin are responsible for the apoptotic activity. In the case of colon cancer cells, Cheng et al (2011) have demonstrated that treatment of HT-29 human colon cancer cells with temperature modified HG-rich pectin dramatically increased anti-proliferative effect in the cells.…”

Galacturonosyltransferase (GAUT)1 and GAUT7 are the core of a plant cell wall pectin biosynthetic homogalacturonan:galacturonosyltransferase complex

“…They provide structural support in primary walls, influence secondary wall formation in fibers and woody tissues, and are a reservoir of oligosaccharide signaling molecules (1,(7)(8)(9). The gelling and stabilizing properties of pectin are exploited for food enhancement and industrial purposes, and pectin has multiple health benefits including lowering cholesterol and serum glucose levels, inhibiting cancer growth and metastasis, and prebiotic function in the gut (10)(11)(12)(13).…”