METHODS: Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex.
RESULTS: Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites.
CONCLUSIONS: Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex.
方法:这里,我们使用体外和计算机模拟方法来测试大黄酚的能力,一种天然来源的分子,通过靶向KITENIN/ErbB4复合物抑制结直肠癌的进展。
结果:大黄酚与ErbB4结合,破坏ErbB4/KITENIN复合物并引起KITENIN的自噬降解。根据分子对接模型,我们证明了大黄酚与ErbB4结合。大黄酚逆转KITENIN介导的细胞运动效应,有氧糖酵解,和下游效应基因的表达。此外,在KITENIN过表达的条件下,大黄酚抑制癌代谢物的产生。
结论:大黄酚通过靶向KITENIN/ErbB4复合物抑制致癌活性。