关键词: MMP−2/9 PI3K/AKT/mTOR pathway fucoxanthin human pharyngeal squamous cell carcinoma metastatic proliferation

Mesh : Humans TOR Serine-Threonine Kinases / metabolism Xanthophylls / pharmacology chemistry Proto-Oncogene Proteins c-akt / metabolism Cell Proliferation / drug effects Signal Transduction / drug effects Phosphatidylinositol 3-Kinases / metabolism Cell Line, Tumor Cell Movement / drug effects Pharyngeal Neoplasms / drug therapy pathology metabolism Carcinoma, Squamous Cell / drug therapy metabolism pathology Neoplasm Metastasis Molecular Docking Simulation

来  源:   DOI:10.3390/molecules29153603   PDF(Pubmed)

Abstract:
Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.
摘要:
人类咽鳞状细胞癌(HPSCC)是头颈部最常见的恶性肿瘤,以高死亡率和转移倾向为特征。岩藻黄质,从褐藻中分离出的类胡萝卜素,表现出与抑制肿瘤增殖和转移相关的药理学特性。然而,其抑制HPSCC增殖和转移的潜力尚未完全阐明。这项研究首次探索了岩藻黄质对两种人咽鳞癌细胞系(FaDu和Detroit562)的抑制作用,以及这些影响的潜在机制。结果显示增殖的剂量依赖性减少,迁移,岩藻黄质处理后HPSCC细胞的侵袭能力。进一步研究表明,岩藻黄质导致磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素机制靶标(mTOR)途径中蛋白质的表达水平显着降低,以及下游蛋白基质金属蛋白酶(MMP)-2和MMP-9。PI3K/AKT的特异性激活剂逆转了岩藻黄质对这些蛋白质的作用,以及细胞增殖和转移,在FaDu和底特律562细胞中。分子对接实验证实岩藻黄质与PI3K有强烈的相互作用,AKT,mTOR,MMP-2和MMP-9。总的来说,岩藻黄质,功能性食品成分,是HPSCC的潜在治疗剂。
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