Xie Peiyu, Fujii Isao, Zhao Jien, Shinohara Makoto, Matsukura Makoto
Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0822, Japan.
Ashikita Institution for Developmental Disabilities, Ashikita-machi, Kumamoto 869-541, Japan.
Int J Oncol. 2016 Oct;49(4):1561-1568. doi: 10.3892/ijo.2016.3658. Epub 2016 Aug 18.
In recent years, interest in biological activities of compounds from marine organisms has intensified. Cancer is the most principal enemy for human life and health. For the first time, to the best of our knowledge, we investigated a novel algae-derived polysaccharide for its role in inducing apoptosis and cell cycle arrest in human gastric carcinoma MKN45 cells. We found that the novel polysaccharide suppressed MKN45 cell proliferation, induced cell apoptosis and arrested the cells at G2/M phase. Furthermore, we observed that the generation of reactive oxygen species (ROS) and the phosphorylation of Jun N-terminal kinase (JNK), p53, caspase-9 and -3 were induced in the polysaccharide-treated MKN45 cells. In addition, pretreatment with N-acetyl-cysteine (NAC) and SP600125, the inhibitor of ROS and JNK, induced MKN45 cell proliferation, prevented the cell apoptosis and released the cells from cycle arrest. Finally, we found that pretreatment with NAC prevented the JNK, p53, caspase-9 and -3 protein phosphorylation induced by the polysaccharide, however, pretreatment with SP600125 did not affect the generation of ROS, suggesting that ROS is upstream of JNK. Taken together, the novel polysaccharide induced cancer cell apoptosis and arrested cell cycle via ROS/JNK signaling pathway.
近年来，人们对海洋生物化合物的生物活性的兴趣日益浓厚。癌症是人类生命和健康的最主要敌人。据我们所知，我们首次研究了一种新型藻类衍生多糖在诱导人胃癌MKN45细胞凋亡和细胞周期停滞中的作用。我们发现这种新型多糖抑制了MKN45细胞的增殖，诱导了细胞凋亡，并使细胞停滞在G2/M期。此外，我们观察到在多糖处理的MKN45细胞中诱导了活性氧（ROS）的产生以及Jun N端激酶（JNK）、p53、半胱天冬酶-9和-3的磷酸化。此外，用N-乙酰半胱氨酸（NAC）和ROS及JNK的抑制剂SP600125预处理可诱导MKN45细胞增殖，防止细胞凋亡并使细胞从周期停滞中释放出来。最后，我们发现用NAC预处理可防止多糖诱导的JNK、p53、半胱天冬酶-9和-3蛋白磷酸化，然而，用SP600125预处理并不影响ROS的产生，这表明ROS在JNK的上游。综上所述，这种新型多糖通过ROS/JNK信号通路诱导癌细胞凋亡并使细胞周期停滞。
