Jing-Gung Chung1, Jureerut Daduang2, Pornsuda Maraming3, Sompong Klaynongsruang4, Patcharee Boonsiri5, Shu-Fen Peng6,7, Sakda Daduang8, Prapenpuksiri Rungsa8, Ratree Tavichakorntrakool9. 1. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.; jurpoo@kku.ac.th jgchung@mail.cmu.edu.tw. 2. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand jurpoo@kku.ac.th jgchung@mail.cmu.edu.tw. 3. Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand. 4. Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand. 5. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 6. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C. 7. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C. 8. Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand. 9. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Abstract
BACKGROUND/AIM: KT2 is a lysine/tryptophan-rich peptide modified from Crocodylus siamensis Leucrocin I. In this study, we examined the cell toxicity, cellular uptake, anti-migration and anti-invasion activities of KT2 in A375.S2 human melanoma cells. MATERIALS AND METHODS: A375.S2 cells were treated with KT2 peptide and then we performed MTT assay, study of cellular uptake by a confocal microscope, wound healing assay, transwell migration/invasion assay, and evaluation of the expression of metastasis-associated proteins. RESULTS: KT2 can be internalized through the plasma membrane and can slightly alter cell morphology, decrease the percentage of viable cells and inhibit cell migration and invasion of A375.S2 cells in a dose-dependent manner. This peptide suppressed MMP-2 activity, as measured by gelatine zymography assay. The protein level of MMP-2 was decreased by KT2. KT2 also down-regulated metastasis pathway-related molecules, including FAK, RhoA, ROCK1, GRB2, SOS-1, p-JNK, p-c-Jun, PI3K, p-AKT (Thr308), p-AKT (Ser473), p-p38, MMP-9, NF-kB, and uPA. CONCLUSION: These results indicate that KT2 inhibits the migration and invasion of human melanoma cells by decreasing MMP-2 and MMP-9 expression through inhibition of FAK, uPA, MAPK, PI3K/AKT NF-kB, and RhoA-ROCK signalling pathways. These findings suggest that KT2 deserves further investigation as an anti-metastatic agent for human melanoma. Copyright
BACKGROUND/AIM: KT2 is a lysine/tryptophan-rich peptide modified from Crocodylus siamensisLeucrocin I. In this study, we examined the cell toxicity, cellular uptake, anti-migration and anti-invasion activities of KT2 in A375.S2humanmelanoma cells. MATERIALS AND METHODS:A375.S2 cells were treated with KT2 peptide and then we performed MTT assay, study of cellular uptake by a confocal microscope, wound healing assay, transwell migration/invasion assay, and evaluation of the expression of metastasis-associated proteins. RESULTS: KT2 can be internalized through the plasma membrane and can slightly alter cell morphology, decrease the percentage of viable cells and inhibit cell migration and invasion of A375.S2 cells in a dose-dependent manner. This peptide suppressed MMP-2 activity, as measured by gelatine zymography assay. The protein level of MMP-2 was decreased by KT2. KT2 also down-regulated metastasis pathway-related molecules, including FAK, RhoA, ROCK1, GRB2, SOS-1, p-JNK, p-c-Jun, PI3K, p-AKT (Thr308), p-AKT (Ser473), p-p38, MMP-9, NF-kB, and uPA. CONCLUSION: These results indicate that KT2 inhibits the migration and invasion of humanmelanoma cells by decreasing MMP-2 and MMP-9 expression through inhibition of FAK, uPA, MAPK, PI3K/AKT NF-kB, and RhoA-ROCK signalling pathways. These findings suggest that KT2 deserves further investigation as an anti-metastatic agent for humanmelanoma. Copyright
Authors: M W Lee; R Bassiouni; N A Sparrow; A Iketani; R J Boohaker; C Moskowitz; P Vishnubhotla; A S Khaled; J Oyer; A Copik; C Fernandez-Valle; J M Perez; A R Khaled Journal: Cell Death Dis Date: 2014-05-22 Impact factor: 8.469
Authors: Aneta Gandalovičová; Daniel Rosel; Michael Fernandes; Pavel Veselý; Petr Heneberg; Vladimír Čermák; Luboš Petruželka; Sunil Kumar; Victoria Sanz-Moreno; Jan Brábek Journal: Trends Cancer Date: 2017-06