G2 cell cycle arrest and apoptosis are induced in Burkitt's lymphoma cells by the anticancer agent oracin.
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%).
Klucar
J
J
Centre for Biochemical Engineering, School of Chemical Engineering, University of Birmingham, Edgbaston, UK.
Al-Rubeai
M
M
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
D000970:Antineoplastic Agents; D004983:Ethanolamines; D007546:Isoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; C103439:oracine