A novel androstenedione derivative induces ROS-mediated autophagy and attenuates drug resistance in osteosarcoma by inhibiting macrophage migration inhibitory factor (MIF)

• DOI: 10.1038/cddis.2014.300
• Publication Date: 2014-08-07T13:14:57Z
• Authors: Y Liu; L Zhao; Y Ju; W Li; M Zhang; Y Jiao; J Zhang; S Wang; Y Wang; M Zhao; B Zhang; Y Zhao
• Keywords: 0301 basic medicine; Osteosarcoma; Adenine; Androstenedione; Down-Regulation; Bone Neoplasms; Translocation, Genetic; Acetylcysteine; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Drug Resistance, Neoplasm; Cell Line, Tumor; Autophagy; Humans; Secosteroids; Original Article; RNA Interference; HMGB1 Protein; RNA, Small Interfering; Reactive Oxygen Species; Macrophage Migration-Inhibitory Factors

Osteosarcoma is a common primary bone tumor in children and adolescents. The drug resistance of osteosarcoma leads to high lethality. Macrophage migration inhibitory factor (MIF) an inflammation-related cytokine implicated the chemoresistance breast cancer. In this study, we isolated novel androstenedione derivative identified as 3,4-dihydroxy-9,10-secoandrosta-1,3,5,7-tetraene-9,17-dione (DSTD). DSTD could inhibit MIF expression MG-63 U2OS cells. inhibition by promoted autophagy inducing Bcl-2 downregulation translocation HMGB1. N-acetyl-L-cysteine (NAC) 3-methyladenine (3-MA) attenuated DSTD-induced but cell death, suggesting that induced ROS-mediated rescue death. However, presence chemotherapy drugs, enhanced chemosensitivity decreasing HMGB1 level. Our data suggest therapeutic strategy for overcoming osteosarcoma.