Detection of apoptosis in KG-1a leukemic cells treated with investigational drugs

Four investigational drugs, p-benzoquinone, primine, miconidine acetate, and artesunate (dihydroqinghaosusuccinate), with growth inhibitory activity against flagellatae (e.g. trypanosoma, leptomonas, plasmodium) were investigated for their capability to induce programmed cell death (apoptosis) in human KG-1a leukemic cells. The results were compared with those of three well established cytostatic agents (cisplatin, daunorubicin, cytosine-arabinoside) and ionizing radiation. The antitumor activity of the drugs was validated by a cellular growth inhibition assay. The depletion of glutathione by these four investigational drugs favours the hypothesis that formation of free radicals and subsequent DNA strand breaks may be critical mechanisms of action and that the glutathione redox cycle is involved in detoxification of these reactive molecules.