Kim Suhyeon, Na MinKyun, Oh Sangtaek
Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
J Microbiol Biotechnol. 2025 Jul 18;35:e2503050. doi: 10.4014/jmb.2503.03050.
Molecular irregularities in the canonical Wnt pathway that lead to the stabilization of β-catenin are common in colon cancer. Here, we identified 1,2,3,6-Tetra-O-galloyl-β-D-glucopyranose (TAGP), separated from , as an inhibitor of canonical Wnt signaling. TAGP facilitated the phosphorylation of Ser33/37 and the degradation of β-catenin, which had accumulated due to Wnt3a-conditioned medium or the inhibitor 6-bromoindirubin-3'-oxime that targets glycogen synthase kinase-3β (GSK-3β). Additionally, TAGP lowered the levels of Cyclin D1 and c-Myc, which are regulated by β-catenin/T-cell factor (TCF) and showed antiproliferative activity in colon cancer cells. Furthermore, TAGP triggered apoptosis, as demonstrated by the activation of caspases 3 and 7, in conjunction with raising the number of Annexin-V-positive cells. It also promoted ferroptosis, as shown by the buildup of lipid peroxides and Fe in the cells. Taken together, TAGP enhances β-catenin turnover, indicating its potential as a chemotherapeutics for colon cancer in humans.
导致β-连环蛋白稳定的经典Wnt信号通路中的分子异常在结肠癌中很常见。在这里，我们从[具体来源未提及]中分离出1,2,3,6-四-O-没食子酰基-β-D-吡喃葡萄糖（TAGP），作为经典Wnt信号传导的抑制剂。TAGP促进了Ser33/37的磷酸化以及β-连环蛋白的降解，β-连环蛋白因Wnt3a条件培养基或靶向糖原合酶激酶-3β（GSK-3β）的抑制剂6-溴靛玉红-3'-肟而积累。此外，TAGP降低了细胞周期蛋白D1和c-Myc的水平，它们受β-连环蛋白/T细胞因子（TCF）调节，并在结肠癌细胞中显示出抗增殖活性。此外，TAGP引发了细胞凋亡，这通过半胱天冬酶3和7的激活以及膜联蛋白-V阳性细胞数量的增加得以证明。它还促进了铁死亡，表现为细胞内脂质过氧化物和铁的积累。综上所述，TAGP增强了β-连环蛋白的周转，表明其作为人类结肠癌化疗药物的潜力。
