Curcumin Analogue L48H37 Suppresses Human Osteosarcoma U2OS and MG-63 Cells' Migration and Invasion in Culture by Inhibition of uPA via the JAK/STAT Signaling Pathway

doi:10.3390/molecules26010030

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23315

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23315

Title:	Curcumin Analogue L48H37 Suppresses Human Osteosarcoma U2OS and MG-63 Cells' Migration and Invasion in Culture by Inhibition of uPA via the JAK/STAT Signaling Pathway
Authors:	Lu, KH;Wu, HH;Lin, RC;Lin, YC;Lu, PWA;Yang, SF;Yang, JS
Keywords:	migration;osteosarcoma;JAK;STAT;uPA
Date:	2021
Issue Date:	2022-08-05T09:35:17Z (UTC)
Publisher:	MDPI
Abstract:	Osteosarcoma, the most prevalent malignant bone tumor in the pediatric age group, is responsible for the great majority of cancer-associated deaths owing to its highly metastatic potential. The anti-metastatic effects of the new curcumin analogue L48H37 in human osteosarcoma are still unknown; hence, we investigated whether L48H37 represses human osteosarcoma cells' biological behavior of migratory potential and invasive activities and attempted to delve into its underlying mechanisms. L48H37 up to 5 mu M inhibited, without cytotoxicity, the motility, migration, and invasion of human osteosarcoma U2OS and MG-63 cells. In U2OS cells, the human protease array revealed an obvious decrease in urokinase plasminogen activator (uPA) expression after L48H37 treatment, and L48H37 actually reduced the level, protein and mRNA expression, and promoter activity of uPA dose-dependently. L48H37 decreased the phosphorylation of STAT3, JAK1, JAK2, and JAK3 in U2OS cells, but did not affect the phosphorylation of ERK, JNK, p38, and Akt. Using colivelin, an activator of STAT3, the L48H37-induced decrease in uPA and migratory potential could be countered as expected. Collectively, L48H37 represses the invasion and migration capabilities of U2OS and MG-63 cells by the suppression of uPA expression and the inhibition of JAK/STAT signaling. These results suggest that L48H37 may be a potential candidate for anti-metastatic treatment of human osteosarcoma.
URI:	http://dx.doi.org/10.3390/molecules26010030 https://www.webofscience.com/wos/woscc/full-record/WOS:000606075800001 https://ir.csmu.edu.tw:8080/handle/310902500/23315
Relation:	MOLECULES ,2021,v26,issue 1
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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