G2 cell cycle arrest and apoptosis are induced in Burkitt's lymphoma cells by the anticancer agent oracin

FEBS Letters

Klucar, J¹  Al-Rubeai, M¹ 

[1] Centre for Biochemical Engineering, School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

关键词: Apoptosis;    Cell cycle;    Oracin;    G2 arrest;    bcl-2;    Anticancer agent;   

DOI  :  10.1016/S0014-5793(96)01307-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μmol/l) than for BL SV2 cells (1.0 μmol/l). There was no significant increase in apoptosis after 24 h of treatment with oracin (1.0 μmol/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 μmol/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%).

【 授权许可】

Unknown