title: Isothiocyanates inhibit the invasion and migration of C6 glioma cells by blocking FAK/JNK-mediated MMP-9 expression.
abstract: Isothiocyanates (ITCs) derived from cruciferous vegetables, including benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane (SFN), exhibit preventative effects against various types of cancers. Yet, the inhibitory effects of ITCs on C6 glioma cell invasion and migration have not been reported. Thus, we aimed to analyze ITC-regulated MMP-9 activation, a crucial enzyme of cancer metastasis that degrades the extracellular matrix, in C6 glioma cells to investigate the inhibitory effects on cancer invasion and migration by ITCs. In the present study, we found that ITCs specifically suppressed PMA-induced MMP-9 secretion and protein expression. The inhibitory effects of ITCs on PMA-induced MMP-9 expression were found to be associated with the inhibition of MMP-9 transcription levels through suppression of nuclear translocation of NF-κB and activator protein-1 (AP-1). It was also confirmed that ITCs decreased MMP-9-mediated signaling such as FAK and JNK, whereas they had no effect on the phosphorylation of ERK and p38. Moreover, wound-healing and Τranswell invasion assays showed that ITCs inhibited the migration and invasion of C6 glioma cells. These results suggest that ITCs could be potential agents for the prevention of C6 glioma cell migration and invasion by decreasing FAK/JNK-mediated MMP-9 expression.
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Chang-Su
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Jae-Moon
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Yoon-Yub
authors.initials: YY
authors.lastname: Park
authors.affiliation: School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Program), Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
authors.affiliation: Department of Biotechnology, Catholic University of Daegu, Gyeongsan 712-702, Republic of Korea.
authors.forename: Il-Kyung
authors.initials: IK
authors.lastname: Chung
authors.affiliation: Department of Physical Therapy, Inje University, Gimhae 621-749, Republic of Korea.
authors.forename: Mihyun
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Kyunggi-Do 440-746, Republic of Korea.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 701-947, Republic of Korea.
authors.forename: Fansi
authors.initials: F
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 701-947, Republic of Korea.
authors.forename: Hyeun-Wook
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage*; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D013454:Sulfoxides; D018808:Transcription Factor AP-1 / Q000235:genetics
chemical_list: D017879:Isothiocyanates; D016328:NF-kappa B; D013454:Sulfoxides; D018808:Transcription Factor AP-1; C058305:phenethyl isothiocyanate; C031403:benzyl isothiocyanate; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048670:MAP Kinase Kinase 4; D020780:Matrix Metalloproteinase 9; C016766:sulforaphane