title: Tianeptine sodium salt suppresses TNF-α-induced expression of matrix metalloproteinase-9 in human carcinoma cells via suppression of the PI3K/Akt-mediated NF-κB pathway.
abstract: Tianeptine sodium salt (TSS) is a selective facilitator of serotonin, but there are no reports regarding anti-invasive effects of TSS. Therefore, we investigated the effect of TSS on the expression of matrix metalloproteinase-9 (MMP-9) and invasion in three different human carcinoma cell lines. Our findings showed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α), and that TSS reduced TNF-α-induced MMP-9 activity in a dose-dependent manner. TSS also downregulated both MMP-9 expression and TNF-α-induced MMP-9 promoter activity. Using a matrigel invasion assay, we showed that TSS significantly attenuated invasive rates in TNF-α-stimulated LNCaP prostate carcinoma cells. Furthermore, TSS suppressed TNF-α-induced NF-κB activity, which is a potential transcriptional factor for regulating many invasive genes, including MMP-9, by suppressing IκB degradation and nuclear translocation of NF-κB subunits in LNCaP prostate carcinoma cells. TSS also downregulated TNF-α-induced phosphorylation of phosphatidyl-inositol 3 kinase (PI3K) and Akt, and a selective PI3K/Akt inhibitor, LY294002, diminished TNF-α-induced NF-κB activation followed by levels of MMP-9, suggesting that TSS also reduces MMP-9 expression by inhibiting the PI3K/Akt-mediated NF-κB pathway. These results indicate that TSS is a potential anti-invasive agent by suppression of TNF-α-induced MMP-9 expression via inhibition of PI3K/Akt-mediated NF-κB activity.
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Rajapaksha Gedara Prasad Tharanga
authors.initials: RG
authors.lastname: Jayasooriya
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Matharage Gayani
authors.initials: MG
authors.lastname: Dilshara
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-051, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Chungbuk, Cheongju 361-763, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: immunkim@jejunu.ac.kr.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013841:Thiazepines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D013841:Thiazepines; D014409:Tumor Necrosis Factor-alpha; C050504:tianeptine; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Invasion; Matrix metalloproteinase-9; Nuclear factor-κB; Phosphatidyl-inositol 3 kinase/Akt; Tianeptine sodium salt