title: G2 cell cycle arrest and apoptosis are induced in Burkitt's lymphoma cells by the anticancer agent oracin.
abstract: The cytotoxic effect of the new potential intercalating anticancer drug oracin was studied on Burkitt's lymphoma cell line that overexpressed bcl-2 (BL bcl-2) and a control transfectant without the bcl-2 gene (BL SV2). Oracin showed a marked cytostatic effect on both BL SV2 and BL bcl-2 cells. IC50, as measured by the MTT assay, was approx. 5-times greater for BL bcl-2 cells (5.0 micromol/l) than for BL SV2 cells (1.0 micromol/l). There was no significant increase in apoptosis after 24 h of treatment with oracin (1.0 micromol/l) in both cell lines. However, after 48 h from the removal of oracin in BL SV2 culture the levels of apoptotic and secondary necrotic cells increased to 20 and 37%, respectively. In contrast, BL bcl-2 cells treated in a similar manner showed only basal levels of apoptotic and secondary necrotic cells. Analysis of the cell cycle profiles showed a significant increase of S and G2/M phases of the cell cycle in both cell lines after 6 h of drug treatment (1.0 micromol/l). The cells were arrested in G2/M phase of the cell cycle after 24 h, with no significant changes in cell viability. After 72 h, the viable BL SV2 cells were still in G2/M, however, the viability of this culture had fallen to approx. 5%. Flow cytometry analysis of the DNA content revealed the presence of a 'sub-G2' region, which represented the apoptotic cells. The BL SV2 cells died after 72 h while they were in the G2/M phase. Although the treated BL bcl-2 cells were similarly arrested in the G2/M phase, they nevertheless remained with a relatively high viability (68%).
authors.affiliation: Centre for Biochemical Engineering, School of Chemical Engineering, University of Birmingham, Edgbaston, UK.
authors.forename: J
authors.initials: J
authors.lastname: Klucar
authors.forename: M
authors.initials: M
authors.lastname: Al-Rubeai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D004983:Ethanolamines / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000235:genetics / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004983:Ethanolamines; D007546:Isoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; C103439:oracine