Matrix metalloproteinases (MMPs) play a crucial role in tumor angiogenesis, and metastasis. 4′-geranyloxyferulic acid (GOFA) has anti-tumor and anti-inflammatory proprieties. Herein, we aimed to determine whether this compound affects cell survival, invasion, and migration through reactive oxygen species (ROS)-mediated MMPs activation of extracellular signal-regulated kinases (ERKs) and p38 signaling in lymphocytic histiocytoma (U937) and colorectal cancer (HCT116) cells. We observed that lipopolysaccharide (LPS) stimulated U937 and HCT116 cells presented abnormal cell proliferation and increased metalloproteinase (MMP-9) activity and expression. Non-cytotoxic doses of GOFA blunted matrix invasive potential by reducing LPS-induced MMP-9 expression and cell migration via inhibiting ROS/ ERK pathway. GOFA also attenuated apoptosis and cell senescence. Our findings indicate that GOFA, inhibiting cancer cell proliferation and migration, could be therapeutically beneficial to prevent tumor metastasis.

中文翻译：

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4'-Geranyloxyferulic Acid通过MMP-9下调对LPS刺激的U937和HCT116细胞的迁移抑制作用：涉及ROS / ERK信号通路。

基质金属蛋白酶（MMP）在肿瘤血管生成和转移中起关键作用。4'-香叶基氧基阿魏酸（GOFA）具有抗肿瘤和抗炎的特性。本文中，我们旨在确定该化合物是否通过淋巴细胞中的组织细胞瘤（U937）和结直肠癌中的活性氧（ROS）介导的MMP激活细胞外信号调节激酶（ERKs）和p38信号传导来影响细胞存活，侵袭和迁移（ HCT116）细胞。我们观察到脂多糖（LPS）刺激U937和HCT116细胞呈现异常的细胞增殖和增加的金属蛋白酶（MMP-9）活性和表达。GOFA的非细胞毒性剂量通过降低LPS诱导的MMP-9表达和通过抑制ROS / ERK途径的细胞迁移而削弱了基质侵袭能力。GOFA还减弱了细胞凋亡和细胞衰老。我们的发现表明，GOFA抑制癌细胞的增殖和迁移，在预防肿瘤转移方面可能具有治疗优势。