Lonidamine is a selective inhibitor that inhibits aerobic glycolysis in murine tumor cells. Lonidamine at a concentration of 0.32mM reduced the respiration of germ cells and submaxillary gland cells by 58%. Treatment of Serotoli’s cells and hepatocytes with lonidamine led to 16% and 6% inhibition of oxygen consumption, respectively. Lonidamine at the same concentration inhibited oxygen consumption of Ehrlich ascites tumor cells and sarcoma 180 cells by 58 and 63%, respectively, but enhanced aerobic glycolysis in normal cells, such as germ cells (57%) and submaxillary gland cells (35%). Lonidamine at a concentration of 20mM reduced the amount of glucose 6-phosphate formed by the mitochondria of Ehrlich ascites tumor cells by >50%.[2] Lonidamine inhibited glioma cell proliferation with an IC50 value of 200μM. Treatment of SNb-19 cells with 100 or 200μM lonidamine resulted in a slight decrease in the S-phase component of the cell cycle (3% and 9%, respectively). The administration of nude mice with lonidamine (160 mg/kg body weight/day) and diazepam (1 mg/kg body weight/day) via intraperitoneal injection for 10 days inhibited the growth of TG-8-OZ glioma xenograft (78% inhibition) 7 days after the treatment.[1]
作用机制
Lonidamine is a derivative of indazole-3-carboxylic acid that affects energy metabolism in tumor cells by inhibiting mitochondria-bound hexokinase and the electron transport chain.[1]
搜索
