title: Timosaponin AIII inhibits migration and invasion of A549 human non-small-cell lung cancer cells via attenuations of MMP-2 and MMP-9 by inhibitions of ERK1/2, Src/FAK and β-catenin signaling pathways.
abstract: Timosaponin AIII (TAIII) is a type of steroidal saponins isolated from Anemarrhena asphodeloides. It was known to improve learning and memory deficits through anti-inflammatory effects. TAIII was also reported to induce autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells and inhibit the growth of human colorectal cancer cells, thus regarded as a potential candidate for anti-cancer agent. In this study, we verified apoptosis-inducing and cell-cycle-arresting effects of TAIII in A549 human non-small-cell lung cancer (NSCLC) cells. Then, we report that TAIII suppresses migration and invasion of A549 human NSCLC cells. We propose that two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, which are well known to be involved in cancer-metastasis, are attenuated by the treatment of TAIII. TAIII exerts its suppressive effects on MMP-2 and MMP-9 via inhibitions of ERK1/2, Src/FAK and β-catenin signalings which are closely related with the regulations of MMP-2 and MMP-9.
authors.affiliation: Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam, Gyeonggi 461-701, Republic of Korea.
authors.forename: Okkeun
authors.initials: O
authors.lastname: Jung
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam, Gyeonggi 461-701, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Yun
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon, Jeonnam 530-742, Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-Do 426-791, Republic of Korea.
authors.forename: Chongsuk
authors.initials: C
authors.lastname: Ryou
authors.affiliation: Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam, Gyeonggi 461-701, Republic of Korea. Electronic address: leesaye@gachon.ac.kr.
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000072283:A549 Cells; D031403:Anemarrhena / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012503:Saponins / Q000737:chemistry* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects*; D013256:Steroids / Q000737:chemistry* / Q000633:toxicity; D051176:beta Catenin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D012503:Saponins; D013256:Steroids; D051176:beta Catenin; C543146:timosaponin AIII; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: ERK1/2; FAK; Human non-small-cell lung cancer; Matrix metalloproteinases; Metastasis; Src; Timosaponin AIII