ANTITUMOR AGENT-INDUCED APOPTOSIS IN MYELOID-LEUKEMIA CELLS - A CONTROLLED SUICIDE

Traditional antitumor research has generally believed that the cytotox icity of antitumor agents was directly correlated with the amount of d rug-induced cellular lesions. Accordingly, oncologists have tried to i mprove anticancer agent/target interactions by increasing the intracel lular dose of active effecters. However, a growing body of evidence st emming from both clinical and experimental observations, strongly sugg ests that similar anticancer-induced lesions may result in different c ellular responses, greatly influencing cytotoxicity. For example, it h as been shown that in some but not all cellular models, antitumor agen ts trigger apoptosis, an irreversible process which leads to a rapid a nd complete elimination of tumor cells. Several of these studies also demonstrated that apoptosis induced by antitumor agents is highly regu lated by multiple signaling pathways which are themselves influenced b y oncogenes, protein kinase activities, external stimuli and the oxida tive balance. Therefore, it appears that cell death commitment is cont rolled by both external and internal factors which interfere downstrea m of drug-or ionizing radiation-target interaction. The characterizati on of these mediators may provide novel strategies for modulating intr acellular signaling pathways in order to promote apoptosis in drug-res istant tumor cells.