Research for natural compounds inducing apoptosis in leukemia cells without foxicity on normal immune cells.

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Hematotoxic side effects including myelotoxicity or immunotoxicity seriously prevent beneficial application of chemotherapeutic agents for leukemia, since most of anti-leukemic agents cause necrotic cell death in normal cells of the host. In the present study, I have developed a screening system which can select out compounds exibiting antileukemia activity against human promyelocytic leukemia HL-60 cells or human T lymphocytic leukemia MOLT-4 cells without causing toxicity on mitogen-stimulated human lymphocytes. The screening system also includes selection of the compounds having activity to cause apoptosis in leukemia cells.Apoptosis was detected with agarose gel electrophoresis, cell death detection ELISA,and flow cytometry. Among approximately 100 naturally-occurring compounds tested, I have discovered some compounds exhibiting apoptosis-inducing activity selectively against HL-60 cells without causing lymphocytotoxicity. Tangeretin, a pentamethoxyflavone from tangerine peer showed strong cytostatic activity on HL-60 cell growth in vitro and apoptosis-inducing ability without causing necrosis in mitogen-stimulated human peripheral-blood lymphocytes. Thus, the data suggest possible efficacy of tangeretin as a candidate for antileukemic agent with novel mechanism and low immunotoxicity.