title: Maclurin suppresses migration and invasion of human non-small-cell lung cancer cells via anti-oxidative activity and inhibition of the Src/FAK-ERK-β-catenin pathway.
abstract: Recent reports indicated that ROS is closely related with cancer metastasis. ROS targets major signaling molecules which are known to be involved in migration and invasion of cancer cells. Here we report that maclurin, a major phenolic component of ethanol extracted mulberry twigs, exerts anti-metastatic effect in A549 human non-small-cell lung cancer cells. Maclurin suppresses intracellular ROS level in A549 human non-small-cell lung cancer cells. Also, maclurin down-regulates Src and ERK, which are well known to be regulated with redox state. Suppressed Src/FAK and ERK signalings activate GSK3-β, thus inhibiting nuclear accumulation of β-catenin. As a result, transcriptional expressions of two major gelatinases (MMP-2 and MMP-9) were significantly down-regulated. Consequently, migration and invasion of A549 human non-small-cell lung cancer cells were attenuated. Anti-metastatic effect of maclurin on A549 human non-small-cell lung cancer cells were diminished by the treatment of hydrogen peroxide, thus further implicating that the effect of maclurin may be strongly related with its anti-oxidative activity. Thus, our data indicate that the anti-metastatic effect of maclurin is exerted by anti-oxidative activity and inhibition of Src/FAK-ERK-β-catenin signaling pathway.
authors: Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 461-701, Korea.
authors: Min Jung
authors: MJ
authors: Ku
authors: Ji Hyun
authors: JH
authors: Kim
authors: Jongsung
authors: J
authors: Lee
authors: Jae Youl
authors: JY
authors: Cho
authors: Taehoon
authors: T
authors: Chun
authors: Sang Yeol
authors: SY
authors: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D037121:Plant Lectins / Q000494:pharmacology*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; C495270:CTNNB1 protein, human; D037121:Plant Lectins; D051176:beta Catenin; C034551:maclurin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases
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