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Antiproliferative and Antimetastatic Effects of Praeruptorin C on Human Non–Small Cell Lung Cancer through Inactivating ERK/CTSD Signalling Pathways
Molecules ( IF 4.2 ) Pub Date : 2020-04-01 , DOI: 10.3390/molecules25071625
Chien-Ming Liu , Huan-Ting Shen , Yi-An Lin , Yung-Luen Yu , Yong-Syuan Chen , Chung-Jung Liu , Yi-Hsien Hsieh

Praeruptorin C (PC) reportedly has beneficial effects in terms of antiinflammation, antihypertension, and antiplatelet aggregation, and it potentially has anticancer activity. However, the effect of PC on human non–small cell lung cancer (NSCLC) is largely unknown. Compared with the effects of praeruptorin A and praeruptorin B, we observed that PC significantly suppressed cell proliferation, colony formation, wound closure, and migration and invasion of NSCLC cells. It induced cell cycle arrest in the G0/G1 phase, downregulated cyclin D1 protein, and upregulated p21 protein. PC also significantly reduced the expression of cathepsin D (CTSD). In addition, the phosphorylation/activation of the ERK1/2 signalling pathway was significantly suppressed in PC-treated NSCLC cells. Cotreatment with PC and U0126 synergistically inhibited CTSD expression, cell migration, and cell invasion, which suggests that the ERK1/2 signalling pathway is involved in the downregulation of CTSD expression and invasion activity of NSCLC cells by PC. These findings are the first to demonstrate the inhibitory effects of PC in NSCLC progression. Therefore, PC may represent a novel strategy for treating NSCLC.

中文翻译:

Praeruptorin C 通过灭活 ERK/CTSD 信号通路对人非小细胞肺癌的抗增殖和抗转移作用

据报道,Praeruptorin C (PC) 在抗炎、抗高血压和抗血小板聚集方面具有有益作用,并且具有潜在的抗癌活性。然而,PC 对人类非小细胞肺癌 (NSCLC) 的影响在很大程度上是未知的。与praeruptorin A和praeruptorin B的作用相比,我们观察到PC显着抑制NSCLC细胞的细胞增殖、集落形成、伤口闭合以及迁移和侵袭。它在 G0/G1 期诱导细胞周期停滞,下调细胞周期蛋白 D1 蛋白,上调 p21 蛋白。PC 还显着降低了组织蛋白酶 D (CTSD) 的表达。此外,在 PC 处理的 NSCLC 细胞中,ERK1/2 信号通路的磷酸化/激活被显着抑制。与 PC 和 U0126 共同处理协同抑制 CTSD 表达,细胞迁移和细胞侵袭,这表明 ERK1/2 信号通路参与了 PC 对 NSCLC 细胞的 CTSD 表达和侵袭活性的下调。这些发现首次证明了 PC 对 NSCLC 进展的抑制作用。因此,PC 可能代表一种治疗 NSCLC 的新策略。
更新日期:2020-04-01
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