A newly synthesized oleanolic acid derivative inhibits the growth of osteosarcoma cells in vitro and in vivo by decreasing c-MYC-dependent glycolysis

Osteosarcoma (OS) is the primary malignant bone tumor with a peak incidence in children and adolescents. However, the little molecular mechanism of pathogenesis has been known and it is urgent to develop new therapeutical strategies to improve outcomes for patients. CDDO-NFM (N-formylmorpholine substituent of CDDO) is a newly synthesized triterpenoid, which is a derivative of oleanolic acid. In this study, we explored whether CDDO-NFM possesses a potential antitumor effect and revealed its molecular mechanism. We found that CDDO-NFM efficiently inhibited cell growth of OS cells and this inhibitory effect was independent of apoptosis-related and cell-cycle–related proteins. CDDO-NFM could decrease the level of glucose uptake, the generation of lactate, and the production of adenosine triphosphate to block the process of glycolysis. In vitro and in vivo cell-based assays showed that CDDO-NFM inhibited glycolysis via degradation of c-MYC rather than activating peroxisome proliferator-activated receptor gamma. Finally, CDDO-NFM could reduce tumor volume and weight with low toxicity, and down-regulate the expression of glycolysis-related enzymes in nude mice. Taken together, these results showed that CDDO-NFM might be a promising antitumor compound.