Anti-FOXO3 (N-terminal) polyclonal antibody

The outcome of chemotherapy for osteosarcoma have improved during the past decade and more patients have access to combination chemotherapy, but there has been no significant clinical progress in the patient survival rate. Recently, forkhead-box O3 (FOXO3) was identified as a pivotal transcription factor responsible for the transcriptional regulation of genes associated with suppression of cancer. The purpose of the present study was to screen small chemicals activating FOXO3 and elucidate their underlying mechanism. Using a drug discovery platform based on the phosphorylation status of FOXO3 in osteosarcoma cells, mitoxantrone (MTZ), a type of DNA-damaging agent, was selected as a possible FOXO3 activator from the food and drug administration-approved drug library. MTZ treatments significantly inhibited the phosphorylation level of Akt-pS473 and caused nuclear localization of FOXO3 in osteosarcoma cells. MTZ treatment inhibited proliferation in osteosarcoma cells in vitro, whereas silencing FOXO3 potently attenuates MTZ-mediated apoptosis in osteosarcoma cells. Taken together, the results indicated that MTZ induces apoptosis in osteosarcoma cells through an Akt/FOXO3-dependent mechanism.

The present study is focused on the interaction of paraquat with the erythroid system in bone marrow and spleen of mice. Administration of paraquat (10 mg/kg of body weight i.p. on alternate days in C57Bl/6 mice) induced the level of reactive oxygen species in bone marrow (BM) on 7, 14, and 21 day time points but it was unchanged in spleen erythroid cell. A marked induction of CD147 expression in BM and spleen erythroid cells was observed in the paraquat treated mice. Paraquat treatment also modulated the CD47 expression in erythroid cells and its expression level was significantly higher on day 14, 21 and 28 in bone marrow and on day 14 and 21 in spleen. The expression level of mitochondrial potential and antioxidant genes SOD1, SOD2, GPX1 and FOXO3 expression was significantly reduced in BM erythroid cells but a reverse response was seen in spleen. Taken together, this study demonstrates that paraquat treatment modulates ROS production, mitochondrial membrane potential, and oxidative stress markers gene expression in the erythroid systems of C57Bl/6 mice.