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迷迭香酸通过抑制内源性活性氧抑制肺癌细胞迁移和侵袭。

Moscatilin inhibits lung cancer cell motility and invasion via suppression of endogenous reactive oxygen species.

机构信息

Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

Biomed Res Int. 2013;2013:765894. doi: 10.1155/2013/765894. Epub 2013 May 8.

Abstract

Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS), in which hydroxyl radical (OH(∙)) was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397) and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473), whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy.

摘要

肺癌是全球癌症患者死亡的主要原因,其中大多数患者死于转移。迁移和侵袭是癌症具有高转移潜能的先决条件。从泰国兰花铁皮石斛中分离得到的双苄基衍生物莫斯卡汀已被证明对多种癌细胞系具有抗癌作用。然而,关于莫斯卡汀对癌细胞迁移和侵袭的影响知之甚少。本研究表明,非毒性浓度的莫斯卡汀能够抑制人非小细胞肺癌 H23 细胞的迁移和侵袭。莫斯卡汀的抑制作用与内源性活性氧物种 (ROS) 的衰减有关,其中羟基自由基 (OH(∙)) 被确定为抑制丝状伪足形成的主要物质。Western blot 分析还表明,莫斯卡汀下调了激活的粘着斑激酶(磷酸化 FAK,Tyr 397)和激活的 ATP 依赖性酪氨酸激酶(磷酸化 Akt,Ser 473),而它们的亲本形式则没有检测到变化。总之,我们的结果表明莫斯卡汀抑制肺癌细胞运动和侵袭的新分子基础,并证明了这种药物在肺癌治疗中具有有希望的抗转移潜能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c83/3662177/042005870c9b/BMRI2013-765894.001.jpg

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