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

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.     

Cycloartocarpin Inhibits Migration through the Suppression of Epithelial-to-Mesenchymal Transition and FAK/AKT Signaling in Non-Small-Cell Lung Cancer Cells

Lung cancer metastasis is a multifaceted process that accounts for 90% of cancer deaths. According to several studies, the epithelial–mesenchymal transition (EMT) plays an essential role in lung cancer metastasis. Therefore, this study aimed to investigate the potential pharmacological effect of cycloartocarpin on the suppression of metastasis-related behaviors and EMT. An MTT assay was used to examine cell viability. Cell migration was determined using a wound healing assay. Anchorage-independent cell growth was also performed. Western blot analysis was used to identify the key signaling proteins involved in the regulation of EMT and migration. The results found that non-toxic concentrations of cycloartocarpin (10–20 μM) effectively suppressed cell migration and attenuated anchorage-independent growth in H292, A549, and H460 cells. Interestingly, these effects were consistent with the findings of Western blot analysis, which revealed that the level of phosphorylated focal adhesion kinase (p-FAK), phosphorylated ATP-dependent tyrosine kinase (p-AKT), and cell division cycle 42 (Cdc42) were significantly reduced, resulting in the inhibition of the EMT process, as evidenced by decreased N-cadherin, vimentin, and slug expression. Taken together, the results suggest that cycloartocarpin inhibits EMT by suppressing the FAK/AKT signaling pathway, which is involved in Cdc42 attenuation. Our findings demonstrated that cycloartocarpin has antimetastatic potential for further research and development in lung cancer therapy.