Abstract
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease that shows apoptosis resistance. The introduction of imatinib mesylate has revolutionized the treatment of CML, but imatinib resistance may develop at any time and inevitably leads to disease progression. Synadenium umbellatum Pax. belongs to the Euphorbiaceae family and is popularly used in Brazil for the treatment of cancer. The cytotoxicity of Euphorbiaceae is associated with the ability of these plants and their bioactive compounds to induce apoptotic tumor cell death. Therefore, we aimed to investigate the cytotoxicity and the mechanisms of death induced by S. umbellatum extract in leukemic cells. S. umbellatum cytotoxicity was evaluated by trypan blue exclusion assay and flow cytometric analysis of the cell cycle; the mechanisms involved in K-562 cell death were investigated by light microscopy and flow cytometry. The results demonstrate that S. umbellatum is cytotoxic to leukemic cells in a concentration-dependent manner. Morphological analysis revealed that S. umbellatum treatment induced K-562 cell death by an apoptotic pathway. Furthermore, data indicate ROS overproduction, alterations in mitochondrial membrane potential, phosphatidylserine externalization and activation of caspase 9. Taken together, the results demonstrate that S. umbellatum extract arrested the cell cycle and triggered apoptosis at several levels in K-562 cells.
Highlights
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease driven by the BCR-ABL fusion protein that arises from the translocation of chromosomes 9 and 22
S. umbellatum cytotoxicity was evaluated in the leukemic cell lines, K-562 and Jurkat, by the trypan blue exclusion method, after 24 h of exposure to different concentrations (0.007 - 1 mg/mL)
Differences in the susceptibility of the two leukemic cell lines to S. umbellatum were observed in the IC50 values (IC50 Jurkat = 0.041 mg/mL and IC50 K-562 = 0.073 mg/mL)
Summary
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease driven by the BCR-ABL fusion protein that arises from the translocation of chromosomes 9 and 22. This oncoprotein exhibits constitutively active kinase activity that confers growth potential and apoptosis resistance to CML cells (Cortez, Kadlec, Pendergast, 1995). Imatinib resistance may develop at any time and inevitably leads to disease progression (Fausel, 2007). In this context, new agents are required for the treatment of CML
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