【摘 要】
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Acute promyelocytic leukemia (APL) is a blood cancer characterized by a rapid accumulation of abnormal white blood cells in the bone marrow and blood resulting in anemia,susceptibility to infections,b
【机 构】
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Jackson State University USA
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Acute promyelocytic leukemia (APL) is a blood cancer characterized by a rapid accumulation of abnormal white blood cells in the bone marrow and blood resulting in anemia,susceptibility to infections,bleeding,and hemorrhage.Trisenox (TX)-based chemotherapy has recently been approved by the FDA based on its effectiveness in providing for a complete remission in de novo and relapsed APL patients.Although TX has been reported to induce degradation of PML-RAR alpha protein in these patients,its molecular mechanisms of action against cancer cells remain to be elucidated.In this research,we hypothesize that TX pharmacology is mediated through oxidative stress leading to p53 activation,genotoxicity,and apoptosis in cancer cells.To test this hypothesis,we performed the MTT-assay for cell viability,thiobarbituric acid test for lipid peroxidation,Western Blot analysis for p53 expression,microgel electrophoresis (Comet) assay for genotoxicity,flow cytometry analysis of annexin-5 and caspase-3,and DNA laddering assay for apoptosis,using the human leukemia (HL60) cell line as a test model.MTT assay indicated a strong dose-response relationship with regard to the cytotoxic property of TX.The 24 hr-LD50 was 6.35-± 0.5μg/mL.
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