Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
Department of Agriculture, Forest and Food Sciences, Plant Genetics and Breeding, University of Torino, 10095 Torino, Italy.
Int J Mol Sci. 2022 Aug 1;23(15):8534. doi: 10.3390/ijms23158534.
L. is a wholegrain cereal and an important edible crop. Oats possesses high nutritional and health promoting values and contains high levels of bioactive compounds, including a group of phenolic amides, named avenanthramides (Avns), exerting antioxidant, anti-inflammatory, and anticancer activities. Epidermal growth factor receptor (EGFR) represents one of the most known oncogenes and it is frequently up-regulated or mutated in human cancers. The oncogenic effects of EGFR include enhanced cell growth, angiogenesis, and metastasis, and down-regulation or inhibition of EGFR signaling has therapeutic benefit. Front-line EGFR tyrosine kinase inhibitor therapy is the standard therapy for patients with EGFR-mutated lung cancer. However, the clinical effects of EGFR inhibition may be lost after a few months of treatment due to the onset of resistance. Here, we showed the anticancer activity of Avns, focusing on EGFR activation and signaling pathway. Lung cancer cellular models have been used to evaluate the activity of Avns on tumor growth, migration, EMT, and anoikis induced by EGF. In addition, docking and molecular dynamics simulations showed that the Avns bind with high affinity to a region in the vicinity of αC-helix and the DGF motif of EGFR, jeopardizing the target biological function. Altogether, our results reveal a new pharmacological activity of Avns as EGFR tyrosine kinase inhibitors.
L 是一种全谷物谷物，也是一种重要的食用作物。燕麦具有很高的营养价值和促进健康的价值，并且含有高水平的生物活性化合物，包括一组酚酰胺，称为燕麦酰胺（Avns），具有抗氧化、抗炎和抗癌活性。表皮生长因子受体（EGFR）是最著名的致癌基因之一，在人类癌症中经常过表达或突变。EGFR 的致癌作用包括增强细胞生长、血管生成和转移，而下调或抑制 EGFR 信号转导具有治疗益处。一线 EGFR 酪氨酸激酶抑制剂治疗是 EGFR 突变型肺癌患者的标准治疗方法。然而，由于耐药性的出现，EGFR 抑制的临床效果可能在治疗几个月后丧失。在这里，我们展示了 Avns 的抗癌活性，重点关注 EGFR 的激活和信号通路。已经使用肺癌细胞模型来评估 Avns 对肿瘤生长、迁移、上皮间质转化和 EGF 诱导的失巢凋亡的活性。此外，对接和分子动力学模拟表明，Avns 与 EGFR 的αC-螺旋和 DGF 基序附近的区域具有高亲和力结合，危及靶生物功能。总之，我们的结果揭示了 Avns 作为 EGFR 酪氨酸激酶抑制剂的新的药理学活性。
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