Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells

摘要: B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles re-activation and subsequent expansion. Drugs interfering with cell cycle entry would be greatly beneficial in the treatment this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), most widely prescribed oral hypoglycemic agent, inexpensive well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin apoptotic anti-proliferative activity on leukemic derived patients. Metformin administered vitro either quiescent or activation stimuli, provided by classical co-culturing CD40L-expressing fibroblasts. At doses were totally ineffective normal lymphocytes, induced apoptosis inhibition when stimulated CD40-CD40L ligation. This cytostatic effect accompanied decreased expression survival- proliferation-associated proteins, signaling pathways involved disease progression intracellular glucose available glycolysis. In drug combination experiments, lowered threshold potentiated cytotoxic effects novel molecules. Our results indicate that, while after stimulation are process building full survival cycling armamentarium, presence affects process.