title: Solasodine inhibits invasion of human lung cancer cell through downregulation of miR-21 and MMPs expression.
abstract: Solasodine, a naturally occurring aglycone of glycoalkaloid in eggplant (Solanum melongena), was found to inhibit proliferation in various tumor cells. However, the effect of solasodine on cancer cell metastasis remains unclear. This study investigates the suppression mechanism of solasodine on motility of human lung cancer cell A549 in vitro. Results show that solasodine reduces viability of A549 cells. Treatment with non-toxic doses of solasodine suppresses markedly cell invasion. Solasodine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate that solasodine is effective in suppressing PI3K and Akt phosphorylation. Moreover, solasodine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. Downregulation of miR-21 by miR-21 inhibitor increases RECK expression and decreases cell invasion, suggesting that downregulation of miR-21 by solasodine may contribute to elevate RECK expression and subsequently inhibiting cell invasion. Taken together, the results reveal that inhibition of A549 cell invasion by solasodine may be, at least in part, through blocking MMP expression. Solasodine also reduces PI3K/Akt signaling pathways and downregulates expression of miR-21. These findings demonstrate an attractive therapeutic potential for solasodine in lung cancer anti-metastatic therapy.
authors.affiliation: Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan; Center for General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan; Department of Urology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kun-Hung
authors.initials: KH
authors.lastname: Shen
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
authors.forename: Jui-Hsiang
authors.initials: JH
authors.lastname: Hung
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Weng
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
authors.forename: Ming-Jiuan
authors.initials: MJ
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan, Taiwan. Electronic address: pschen@mail.cnu.edu.tw.
authors.forename: Pin-Shern
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051926:Basigin / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497886:BSG protein, human; D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C115460:RECK protein, human; D012991:Solanaceous Alkaloids; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D051926:Basigin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C012037:solasodine
keywords: Cell invasion; Lung cancer; Matrix metalloproteinase; MicroRNA-21; Solasodine