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 μM 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.
Highlights
Osteosarcoma, mainly arising from the metaphysis of the distal femur or proximal tibia, is the most prevalent bone malignancy, with peak incidence in the second decade of life and the second incidence peak in older adulthood [1,2,3]
These findings indicated that the Janus kinase (JAK)/STAT pathway plays a critical upstream role in L48H37-inhibited migration potential and urokinase-type plasminogen activator (uPA) expression in U2OS cells
These findings indicated that the JAK/STAT pathway plays a critical upstrea7mofro1l2e in L48H37-inhibited migration potential and uPA expression in U2OS cells
Summary
Osteosarcoma, mainly arising from the metaphysis of the distal femur or proximal tibia, is the most prevalent bone malignancy, with peak incidence in the second decade of life and the second incidence peak in older adulthood [1,2,3]. After the EMT of cancer cells, invasion of the basement membrane proceeds through a series of discrete steps, and various proteases predominantly control the degradation of the extracellular matrix (ECM) and the basement membrane of blood and lymph vessels [10]. Of these proteases, urokinase-type plasminogen activator (uPA), matrix metalloproteinase (MMP)-2 (gelatinase A, 72 kDa), and MMP-9 (gelatinase B, 92 kDa) are considered the most crucial enzymes for controlling the degradation of the main constituent of the ECM and are substantially involved in cancer invasion, migration, and metastasis [11,12]. Suppressing uPA-, MMP-2-, or MMP-9-mediated cellular invasion and migration may generate a putative anti-metastasis effect
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
