Jackson Crystal L, Dreaden Tina M, Theobald Lisa K, Tran Nhien M, Beal Tiffany L, Eid Manal, Gao Mu Yun, Shirley Robert B, Stoffel Mark T, Kumar M Vijay, Mohnen Debra
Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, The University of Georgia, Athens, GA 30602, USA.
Glycobiology. 2007 Aug;17(8):805-19. doi: 10.1093/glycob/cwm054. Epub 2007 May 19.
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.
雄激素非依赖性前列腺癌细胞的治疗选择有限。因此，识别能诱导雄激素反应性和雄激素不敏感细胞死亡的药物至关重要。在此我们证明，植物细胞壁的一种产物果胶能够诱导雄激素反应性（LNCaP）和雄激素非依赖性（LNCaP C4-2）人前列腺癌细胞凋亡。通过凋亡检测以及半胱天冬酶-3及其底物聚（ADP-核糖）聚合酶的激活确定，市售分级果胶粉（FPP）在两种细胞系中均诱导了凋亡（比未处理细胞高约40倍）。相反，柑橘果胶（CP）和pH修饰的CP（PectaSol）几乎没有或没有凋亡活性。糖基残基组成和连接分析显示果胶之间没有显著差异。去除酯键的温和碱处理破坏了FPP的凋亡活性，并产生了同型半乳糖醛酸聚糖（HG）寡糖。用果胶甲酯酶去除半乳糖醛酸基羧甲基酯和/或用内切聚半乳糖醛酸酶切割非甲酯化HG对FPP进行处理，并未导致凋亡活性大幅降低，这表明除了羧甲基酯之外还需要一种对碱敏感的连接。对CP进行热处理（HTCP）导致诱导出与FPP相当的显著水平的凋亡，这表明了一种产生凋亡性果胶结构的方法。这些结果表明，果胶中的特定结构元件负责凋亡活性，并且这种结构可以通过对CP进行热处理来产生或富集。这些发现为果胶凋亡活性的机制研究提供了基础，并为开发基于果胶的药物、营养保健品或旨在对抗前列腺癌发生和进展的推荐饮食改变提供了依据。
