Induction of apoptosis in human leukemic U937 cells by tetrandrine.

Tetrandrine, a calcium channel antagonist, is a plant alkaloid possessing various pharmacological activities including anti-tumor activity. We studied tetrandrine to determine whether or not this anti-tumor effect occurs through induction of apoptosis. Tetrandrine inhibited both proliferation and clonogenicity of human leukemic U937 cells at an optimal concentration of 2.5 microg/ml. This growth inhibition was dose and time dependent, and accompanied with evidence of apoptotic changes. The characteristic morphological changes of apoptosis were observed in U937 cells under light microscopy and DNA fragmentation was noted by gel electrophoresis. Moreover, flow cytometric detection of surface phosphatidyl serine expression of U937 cells after treatment with tetrandrine confirmed the induction of apoptosis in these cells. The induction of apoptosis by tetrandrine would appear to proceed via non-Ca2+-dependent pathways.