Histone inhibitor (IOX-1) inhibits osteosarcoma cell stemness and inhibits osteosarcoma cell migration

Abstract

Osteosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Osteosarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The use of combination chemotherapy and surgery enables long-term survival in approximately 60-70% of cases. However, the necessity for surgery, the poor prognosis of patients with metastatic or recurrent disease, and the lack of establishment of chemotherapy suggest that improvements in chemotherapy are desperately needed. Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. IOX1 ((8-Hydroxyquinoline-5-carboxylic acid) as cell-active histone demethylase inhibitors. IOX-1 has been shown to possess numerous biologic activities such as antimalarial, antimicrobial, and anticancer activities. However, the effect of IOX-1 on cell stemness and migration in human osteosarcoma cells is mostly unknown. Here we found that IOX-1 reduced the cell migration of osteosarcoma cancer cells at noncytotoxic concentrations. Sox2, Oct4, and Nanog as the transcription factors required for the induction of cell stemness. We also found that incubation of osteosarcoma cells with IOX-1 reduced Sox2, Oct4, and Nanog mRNA expression. These results will help us to understand the mechanism of IOX-1 in osteosarcoma, and be beneficial for the development of effective anti- osteosarcoma drugs.