Bae Eun Seo, Kim Young-Mi, Kim Dong-Hwa, Byun Woong Sub, Park Hyen Joo, Chin Young-Won, Lee Sang Kook
College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea.
College of Pharmacy, Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Republic of Korea.
Biomol Ther (Seoul). 2020 Sep 1;28(5):465-472. doi: 10.4062/biomolther.2020.003.
Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an -kaurene diterpenoid isolated from , effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.
结直肠癌（CRC）是最具恶性的癌症类型之一，由于包括西方饮食在内的生活方式因素，其发病率正在稳步上升。经典Wnt/β-连环蛋白信号通路的异常激活在结直肠癌发生过程中起重要作用。因此，靶向Wnt/β-连环蛋白信号通路一直被认为是发现用于治疗CRC的小分子的关键策略。在本研究中，我们发现从[具体植物名称]中分离出的贝壳杉烯二萜诺多辛能有效抑制人结肠癌HCT116细胞的增殖。从机制上讲，诺多辛通过Wnt/β-连环蛋白报告基因检测在HEK293和HCT116细胞中有效抑制β-连环蛋白/T细胞因子（TCF）过度激活的转录活性。诺多辛还抑制了HCT116细胞中Wnt/β-连环蛋白靶基因如Axin2、细胞周期蛋白D1和生存素的表达。进一步研究表明，诺多辛较长时间的作用会诱导HCT116细胞的G/M期细胞周期阻滞并随后导致细胞凋亡。这些发现表明，诺多辛在结肠癌细胞中的抗增殖活性可能部分与Wnt/β-连环蛋白信号通路的调节有关。
