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Your search keyword '"Holland, James F"' showing total 14 results
Start Over Author "Holland, James F" Journal cancer research
14 results on '"Holland, James F"'

10. Abstract 2723: Host response to HMTV

Author

Melana, Stella M., primary, Fernandez-Cobo, Mariana, additional, Marin, Tania, additional, Nartey, Teiko, additional, Lee, Ana, additional, Moran, Herberth, additional, Holland, James F., additional, and Pogo, Beatriz GT, additional

Published
2011
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14. Double blockade of cell cycle at g(1)-s transition and m phase by 3-iodoacetamido benzoyl ethyl ester, a new type of tubulin ligand.

Author

Jiang JD, Denner L, Ling YH, Li JN, Davis A, Wang Y, Li Y, Roboz J, Wang LG, Perez-Soler R, Marcelli M, Bekesi G, and Holland JF

Subjects
Animals, Apoptosis drug effects, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology, Drug Screening Assays, Antitumor, Humans, Iodoacetamide analogs & derivatives, Ligands, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Male, Mice, Mice, Nude, Microtubules drug effects, Phosphorylation drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Tubulin metabolism, Tumor Cells, Cultured, Tumor Suppressor Protein p53 biosynthesis, U937 Cells drug effects, Vincristine pharmacology, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Cell Cycle drug effects, Iodoacetamide pharmacology
Abstract

3-Iodoacetamido benzoyl ethyl ester (3-IAABE) is a new compound synthesized in our laboratory. The primary action of 3-IAABE is to inhibit microtubule assembly by interacting with -SH groups on tubulin. In contrast to other known microtubule disrupters, 3-IAABE caused a double blockade in the cell cycle at G(1)-S transition and in M phase. The blockade was determined by cell cycle analysis and chromosome distribution. Kinase activities of cyclin E and cyclin-dependent kinase 2 responsible for the G(1)-S transition were increased, as were the activities of mitotic cyclin B and cdc2. 3-IAABE treatment also increased p53 expression and dephosphorylated (or activated) retinoblastoma protein. Investigation of the signal transduction pathway showed that 3-IAABE induced bcl-2 phosphorylation, followed by activation of caspase-9, -3, and -6, but not caspase-8. DNA fragmentation factor and poly(ADP-ribose) polymerase, the downstream substrates of caspase-3 and -6, were cleaved after 3 h of exposure to 3-IAABE, followed by DNA fragmentation. Pretreatment of the cells with inhibitors of caspase-9, -3, or -6, respectively, inhibited the cleavage of DNA fragmentation factor and poly(ADP-ribose) polymerase and thus inhibited the onset of apoptosis. 3-IAABE showed antitumor activities in the panel of 60 National Cancer Institute human tumor cell lines with total growth inhibition in the range of 0.22-4.3 micro M for solid tumor lines and 0.025-0.22 micro M for leukemia/lymphoma cell lines. The 3-IAABU total growth inhibition of phytohemagglutinin-stimulated healthy human lymphocytes was 450-fold greater than that of leukemic cells. 3-IAABE significantly inhibited the growth of human hepatocarcinoma (BEL-7402) in nude mice by 72% in tumor volume, more strongly than did vincristine (43 percent inhibition). Besides being a novel lead for the design of new anticancer tubulin ligands, the activity of 3-IAABE in the cell cycle may also help us to understand the molecular pharmacology of microtubule-active drugs.

Published
2002

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