Anti-metastatic Effects of Cationic KT2 Peptide (a Lysine/Tryptophan-rich Peptide) on Human Melanoma A375.S2 Cells.

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.

• Authors: Pornsuda Maraming, Sompong Klaynongsruang, Patcharee Boonsiri, Shu-Fen Peng, Sakda Daduang, Prapenpuksiri Rungsa, Ratree Tavichakorntrakool, Jing-Gung Chung, Jureerut Daduang
• Journal: In vivo (Athens, Greece) (In Vivo) 2021 Jan-Feb Vol. 35 Issue 1 Pg. 215-227 ISSN: 1791-7549 [Electronic] Greece
• PMID: 33402468 (Publication Type: Journal Article)
• Copyright: Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Tryptophan
• ROCK1 protein, human
• rho-Associated Kinases
• Matrix Metalloproteinase 2
• Lysine

Topics

• Cell Line, Tumor
• Cell Movement
• Humans
• Lysine
• Matrix Metalloproteinase 2 (genetics)
• Melanoma (drug therapy)
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (genetics)
• Tryptophan
• rho-Associated Kinases