Department of Marine Life Science, Jeju National University, Jeju 63243, Republic of Korea; Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China.
Department of Marine Life Science, Jeju National University, Jeju 63243, Republic of Korea.
Int J Biol Macromol. 2019 Oct 15;139:170-180. doi: 10.1016/j.ijbiomac.2019.07.119. Epub 2019 Jul 20.
The aim of this study was to investigate the antiproliferative effects of fucoidan from three regional hijiki (Hizikia fusiforme) samples (Zhejiang-China, Jeju-Korea [JH], and Wando-Korea) in East Asia. Hijiki was processed using 1% citric acid to decrease heavy metal content. The JH sample was separated using diethylaminoethyl-cellulose-ion exchange chromatography to obtain four active fractions (JHCF1-JHCF4) and their monosaccharide composition was detected using high-performance liquid chromatography. The structure of the crude polysaccharides and four fucoidan fractions was analyzed using Fourier-transform infrared spectroscopy. JHCF4 showed the highest fucose and sulfate content and decreased Hep3B cell growth in 48 h with a half-maximal inhibitory concentration of 33.53 ± 2.50 μg/ml, which represented the strongest anticancer activity. Further, nuclear staining with Hoechst 33342 and acridine orange-ethidium bromide staining demonstrated that the anticancer activity of JHCF4 was mediated by apoptosis. Moreover, JHCF4 down-regulated B-cell lymphoma extra-large, while up-regulating Bcl-2-associated X protein, caspase-3, and apoptotic bodies to different degrees in Hep3B cells. JHCF4 induced apoptosis via the generation of reactive oxygen species along with the concurrent loss of mitochondrial membrane potential, indicating the potential role of the mitochondria-mediated pathway. Therefore, these results indicate that JHCF4 exhibited antiproliferative effects on the investigated cancer cell lines.
本研究旨在探究产自东亚三个地区（中国浙江、韩国济州和韩国莞岛）的羊栖菜褐藻糖胶（fucoidan）的抗增殖作用。羊栖菜经 1%柠檬酸处理以降低重金属含量。济州样本经 DEAE-纤维素离子交换层析分离得到四个活性级分（JHCF1-JHCF4），并采用高效液相色谱法检测其单糖组成。采用傅里叶变换红外光谱法分析了粗多糖和四个褐藻糖胶级分的结构。JHCF4 具有最高的岩藻糖和硫酸根含量，在 48 小时内可使 Hep3B 细胞生长抑制率达到 50%，其半抑制浓度（IC50）为 33.53±2.50μg/ml，表现出最强的抗癌活性。此外，Hoechst 33342 核染色和吖啶橙-溴化乙锭染色表明，JHCF4 的抗癌活性是通过细胞凋亡介导的。而且，JHCF4 下调了 B 细胞淋巴瘤-2 基因家族成员 X（B-cell lymphoma extra-large，Bcl-xl），同时不同程度地上调了 Bcl-2 相关 X 蛋白（Bcl-2-associated X protein，Bax）、半胱天冬酶-3（caspase-3）和凋亡小体。JHCF4 通过生成活性氧和同时损失线粒体膜电位诱导细胞凋亡，表明其潜在的线粒体介导途径的作用。因此，这些结果表明 JHCF4 对所研究的癌细胞系表现出抗增殖作用。
