Ursonic acid inhibits migration and invasion of human osteosarcoma cells through the suppression of mitogen-activated protein kinases and matrix metalloproteinases.

INTRODUCTION: Osteosarcoma (OS) is the most common form of bone malignancy. Although contemporary chemotherapy and surgery have improved the prognosis of those with OS, developing new OS therapies has proven difficult for some time. The activation of the matrix metalloproteinase (MMP) and mitogen-activated protein kinase (MAPK) signaling pathways can induce metastasis, which is an obstacle to OS treatment. Ursonic acid (UNA) is a phytochemical with the potential to cure a variety of human ailments, including cancer. METHODS AND RESULTS: In this study, we investigated the anti-tumor properties of UNA in MG63 cells. We conducted colony formation assay, wound healing assay, and Boyden chamber assays to investigate the anti-OS effects of UNA. UNA was found to significantly inhibit the proliferative, migratory, and invasive abilities of MG63 cells. This bioactivity of UNA was mediated by the inhibition of extracellular signal-regulated kinase (ERK) and p38 and reduction of MMP-2 transcriptional expression as observed in western blot analysis, gelatin zymography and RT-PCR. Anti-OS activities of UNA were also observed in Saos2 and U2OS cells, indicating that its anti-cancer properties are not specific to cell types. CONCLUSION: Our findings suggest that UNA has the potential for use in anti-metastatic drugs in the treatment of OS.

MARS2 drives metabolic switch of non-small-cell lung cancer cells via interaction with MCU.

Mitochondrial methionyl-tRNA synthetase (MARS2) canonically mediates the formation of fMet-tRNAifMet for mitochondrial translation initiation. Mitochondrial calcium uniporter (MCU) is a major gate of Ca2+ flux from cytosol into the mitochondrial matrix. We found that MARS2 interacts with MCU and stimulates mitochondrial Ca2+ influx. Methionine binding to MARS2 would act as a molecular switch that regulates MARS2-MCU interaction. Endogenous knockdown of MARS2 attenuates mitochondrial Ca2+ influx and induces p53 upregulation through the Ca2+-dependent CaMKII/CREB signaling. Subsequently, metabolic rewiring from glycolysis into pentose phosphate pathway is triggered and cellular reactive oxygen species level decreases. This metabolic switch induces inhibition of epithelial-mesenchymal transition (EMT) via cellular redox regulation. Expression of MARS2 is regulated by ZEB1 transcription factor in response to Wnt signaling. Our results suggest the mechanisms of mitochondrial Ca2+ uptake and metabolic control of cancer that are exerted by the key factors of the mitochondrial translational machinery and Ca2+ homeostasis.

Antibacterial capacity of cavity disinfectants against Streptococcus mutans and their effects on shear bond strength of a self-etch adhesive.

We evaluated the antibacterial properties of three disinfectants [2% chlorhexidine (CHX), 6% sodium hypochlorite (NaOCl), and 0.01% urushiol)] against Streptococcus mutans and their effects on bond strength of Scotchbond(TM) Universal. The reduction in bacterial growth was evaluated by the colony counting method. Total 105 specimens were assigned to seven groups, according to surface pretreatment: control group (C) without pretreatment; chlorhexidine gluconate with rinse (CR) or without rinse (CD); NaOCl with rinse (NR) or without rinse (ND); and urushiol with rinse (UR) or without rinse (UD). The shear bond test was performed at a cross-head speed of 0.5 mm/min. None of the disinfected specimens had viable microbes after a 30 min incubation. The control group exhibited the strongest bond; however, no significant difference was detected with the disinfectant-treated groups, except weak bonding with ND group. These findings suggest that all disinfectants tested had strong antibacterial capacity and may better be rinsed away.