Laboratory of Enzyme Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 100-Let Vladivostoku Ave., Vladivostok 690022, Russian Federation.
Mar Drugs. 2013 Jan 21;11(1):194-212. doi: 10.3390/md11010194.
Accumulating data clearly indicate that the induction of apoptosis by nontoxic natural compounds is a potent defense against the development and progression of many malignancies, including colon cancer. Resveratrol and the fucoidans have been shown to possess potent anti-tumor activity in vitro and in vivo. The aim of the present study was to examine whether the combination of a fucoidan from the brown alga Saccharina cichorioides Miyabe and resveratrol would be an effective preventive and/or therapeutic strategy against colon cancer. Based on NMR spectroscopy and MALDI-TOF analysis, the fucoidan isolated and purified from Saccharina cichorioides Miyabe was (1→3)-α-l-fucan with sulfate groups at C2 and C4 of the α-l-fucopyranose residues. The fucoidan enhanced the antiproliferative activity of resveratrol at nontoxic doses and facilitated resveratrol-induced apoptosis in the HCT 116 human colon cancer cell line. Apoptosis was realized by the activation of initiator caspase-9 and effector caspase-7 and -3, followed by the cleavage of PARP. Furthermore, significant inhibition of HCT 116 colony formation was associated with the sensitization of cells to resveratrol by the fucoidan. Taken together, these results demonstrate that the combination of the algal fucoidan with resveratrol may provide a potential therapy against human colon cancer.
越来越多的数据表明,非毒性天然化合物诱导细胞凋亡是预防和控制多种恶性肿瘤(包括结肠癌)发展和恶化的有效手段。白藜芦醇和褐藻糖胶在体外和体内都显示出了强大的抗肿瘤活性。本研究旨在探讨褐藻糖胶与白藜芦醇联合应用是否是一种针对结肠癌的有效预防和/或治疗策略。基于核磁共振光谱和 MALDI-TOF 分析,从褐藻 Saccharina cichorioides Miyabe 中分离和纯化的褐藻糖胶是(1→3)-α-l-岩藻聚糖,其α-l-岩藻糖残基的 C2 和 C4 上带有硫酸基团。褐藻糖胶在非毒性剂量下增强了白藜芦醇的抗增殖活性,并促进了 HCT 116 人结肠癌细胞系中白藜芦醇诱导的细胞凋亡。凋亡是通过起始半胱天冬酶-9 和效应半胱天冬酶-7 和 -3 的激活以及 PARP 的切割来实现的。此外,褐藻糖胶还可显著抑制 HCT 116 集落的形成,从而使细胞对白藜芦醇敏感。综上所述,这些结果表明,褐藻糖胶与白藜芦醇联合应用可能为人类结肠癌的治疗提供一种新的潜在方法。