PO-150 Tomatidine inhibits human osteosarcoma cells metastasis by down-regulation of presenilin-1 and the Raf/MEK/ERK pathway

Abstract

IntroductionTomatidine, the major steroidal alkaloid glycoside presents in the tomato plant, has potent anti-inflammatory and anti-cancer activities. Numerous investigations demonstrated that tomatidine can suppress cancer cell growth and/or induce apoptosis in breast cancer, gastric cancer and lung cancer. However, the effect of tomatidine on human osteosarcoma progression remains uninvestigated. Therefore, we examined the effectiveness of tomatidine against cellular invasion and migration of human osteosarcoma and the underlying mechanisms.Material and methodsAfter treatment with various concentrations of tomatidine, we conducted MTT assay, wound healing assay, Boyden chamber assay, reverse transcription polymerase chain reaction (RT-PCR) and western blot to examine U2OS and HOS human osteosarcoma cell lines.Results and discussionsOur results found that tomatidine significantly reduced motility, migration and invasion without affecting cell proliferation in U2OS and HOS cells. In addition, tomatidine decreased the protein expression of presenilin-1 (PS1), phosphorylation expression in the extracellular signal-regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinase-ERK kinase (MEK), and c-Raf signalling proteins in U2OS and HOS cells. Furthermore, transfection with PS1 siRNA inhibited the migration and invasion capacity of U2OS and HOS cells. Co-treatment with ERK siRNA and tomatidine further reduced U2OS cells migration and invasion.ConclusionThese results indicated that tomatidine inhibits human osteosarcoma U2OS and HOS cells motility, migration and invasion by down-regulating PS1 expressions via c-Raf/MEK/ERK pathways. Tomatidine has the potential to serve as an anti-metastatic agent for treating osteosarcoma.