Pectin induces apoptosis in human prostate cancer cells
Jackson, Crystal Lyles
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Prostate cancer is the most common malignancy and second leading cause of death from cancer in men in the United States. The goal of many cancer therapies, such as androgen deprivation therapy (ADT), is to induce apoptosis in tumor cells. Androgen deprivation therapy in prostate cancer is rarely curative because the metastatic cancer is heterogenous, consisting of both androgen-dependent and androgen-independent prostate cancer cells. Therefore, it is critical to identify agents that induce the death of both androgen-responsive and androgen-insensitive cells. Here it is demonstrated that a product of plant cell walls, pectin, is capable of inducing apoptosis in both androgen-responsive (LNCaP) and androgen-independent (LNCaP C4-2) human prostate cancer cells. Fractionated pectin powder (FPP) induced significant apoptosis (approximately 40-fold above non-treated cells) in both LNCaP and LNCaP C4-2 human prostate cancer cells as determined by the Apoptosense assay and activation of caspase-3 and its substrate, PARP. Citrus pectin and pH-modified pectin, PectaSol, had little or no apoptotic activity, suggesting a structure-dependence to pectin’s apoptotic activity. Glycosyl residue composition and linkage analyses revealed no significant differences between the pectins. Mild base treatment to remove ester linkages destroyed FPP’s apoptotic activity and yielded HGA oligosaccharides. Treatment of FPP with pectinmethylesterase to remove galacturonosyl carboxymethylesters and/or with endopolygalacturonase to cleave non-methylesterified homogalacturonan caused no major reduction in apoptotic activity, implicating the requirement for a base-sensitive linkage other than the carboxymethylester. For the first time, specific structural features of pectin responsible for inducing apoptosis are identified. These findings provide the foundation for future research on the mechanism by which specific pectic structures induce apoptosis in cancer cells and provide a basis for the rational development of pectin-based pharmaceuticals, nutraceuticals, or recommended diet changes aimed at reducing or inhibiting the occurrence and progression of cancer.