Hite, Karen M.2025-01-292025-01-291995-07http://hdl.handle.net/11603/37521The National Cancer Institute (NCI) has been investigating anticancer drugs since its inception. A drug screening program has been part of this drug discovery strategy since 1955. The goal of these efforts has been to identify new candidate drugs and toward clinical efficacy. In the present study, a set identified as having NCI Primary In Vitro for their ability to interesting direct their development of four new lead compounds compound profiles in the Cancer Screen were studied in detail induce cell cycle arrest and induction of apoptosis in a human acute lymphoblastic leukemia cell line, CCRF-CEM. Two of the compounds show a COMPARE pattern typical of known tubulin binding compounds and the other two compounds show striking antileukemia activity. The compound effects were analyzed by flow cytometry for their cell cycle activity. The flow cytometry methodology was first calibrated using a set of five well characterized standard compounds. Standard compounds affecting the cell cycle at the S and G2+M phase and resulting in a reduction of the number of cells in the Gi phase with an accumulation of cells in G2 are represented by vinblastine, ncocdazole and taxol. Hydroxyurea and actinomycin D also affect the cell cycle in S phase, but these compounds block the cells in G1 and S and reduce the number of cells in G2. Flow cytometry analysis indicate that the compounds producing differential anti-leukemia activity have no cell cycle effects, while the putative tubulin inhibitors induced cell cycle arrest resulting in an enrichment of cells in G2. These compounds were also analyzed for their ability to induce apoptosis, by measurement of non-isotypic DNA end extension in situ, CCRF-CEM was shown to express the cell surface apoptosis antigen Fas/Apo-1. The set of compounds characterized by antileukemia activity in the primary screen induced apoptosis in CCRF-CEM cells quantitatively equal to the positive control. The second set of compounds failed to induce apoptosis at any concentration tested.176 pagesen-USText