Morphologic Changes of Apoptosis Induced in Human Chronic Myelogenous Leukemia "Blast" Cells by SC41661A (Searle), A Selective Inhibitor of 5-Lipoxygenase

Authors

K. M. Anderson, Rush Medical College
T. M. Seed, Argonne National Laboratory
J. Peng, Rush Medical College
A. Jajeh, Cook County Hospital
J. Meng, Rush Medical College
J. E. Harris, Rush Medical College

Abstract

Several inhibitors of the arachidonic acid-metabolizing enzyme, 5-lipoxygenase reduce proliferation of hematopoietic and non-hematopoietic cells and cell lines and some cells undergo limited differentiation. Cells were cultured from patients with chronic myelogenous leukemia in "blast" crisis with the selective inhibitor of 5-lipoxygenase,SC41661A[3-{3,5-bis(1,1-dimethyl)-4-hydroxyphenyl}hiol]-N-methyl-N-[2-(2-phridinyl-propanamide)]. Cells cultured for 3 to 5 days with 40 μM SC41661A exhibited reduced cellular numbers along with ultrastructural changes and DNA laddering characteristic of apoptosis. Similar culture conditions reduced proliferation of U937 monoblastoid cells. In U937 cells, the ultrastructural features of apoptosis were not observed at 72 hours, when DNA laddering was present and cell numbers were reduced, but was present after 144 hours of culture. Dissociation between certain morphologic and biochemical sequelae of apoptosis has been described in other systems. These observations are of interest since the induction of apoptosis in dividing chronic myelogenous leukemia (CML) cells by a noncytotoxic agent suggests paradigmatically new sites for therapeutic intervention.

Recommended Citation

Anderson, K. M.; Seed, T. M.; Peng, J.; Jajeh, A.; Meng, J.; and Harris, J. E. (1994) "Morphologic Changes of Apoptosis Induced in Human Chronic Myelogenous Leukemia "Blast" Cells by SC41661A (Searle), A Selective Inhibitor of 5-Lipoxygenase," Scanning Microscopy: Vol. 8: No. 3, Article 24.
Available at: https://digitalcommons.usu.edu/microscopy/vol8/iss3/24