PMID: 11320668Apr 26, 2001Paper

Bisimidazoacridones induce a potent cytostatic effect in colon tumor cells that sensitizes them to killing by UCN-01

Cancer Chemotherapy and Pharmacology
W M CholodyC J Michejda

Abstract

To determine the ability of WMC26, a prototypic bisimidazoacridone (BIA), to induce apoptosis in sensitive colon adenocarcinoma cells and to advance the hypothesis that cancer cells that are growth-arrested by WMC26 are predisposed to undergo apoptotic death by abrogators of cell cycle checkpoints. The antiproliferative activity of WMC26 was examined in detail by a 4-day MTT assay, cell counting, BrdU incorporation and a two-color LIVE/DEAD assay. To detect apoptosis a number of established techniques were used, including gel electrophoresis, flow cytometry, and confocal laser microscopy of treated cells. The activity of senescence-associated beta-galactosidase in treated cells was also analyzed. WMC26, at physiological concentrations, induced complete and longlasting growth arrest of HCT116 cells in culture but did not trigger cell death. The growth-arrested cells (blocked at G1 and G2/M cell cycle checkpoints) did not synthesize DNA but were metabolically active and had intact plasma membranes. Although they resembled the senescence-like phenotype reported to be induced by treatment with some antitumor agents, the cells did not express senescence-associated beta-galactosidase, an indicator of the senescence-like state. Treatm...Continue Reading

Citations

Mar 23, 2007·Bioorganic & Medicinal Chemistry Letters·Deborah L MoodyChristopher J Michejda
Jan 5, 2002·Journal of Clinical Laser Medicine & Surgery
Oct 18, 2005·Molecular Cancer Therapeutics·Teresa Kosakowska-CholodyChristopher J Michejda
Oct 18, 2007·Journal of Medicinal Chemistry·Humcha K HariprakashaChristopher J Michejda
Jun 25, 2005·Journal of Medicinal Chemistry·Wieslaw M CholodyChristopher J Michejda

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