Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells.
Bisacylimidoselenocarbamate derivatives (BSC) are potent anticancer agents with a strong cytotoxic activity against different types of tumour cells. Based in phosphatidylserine exposure on the cell membranes we show that BSC treatment resulted in enhanced cell death in leukaemia CCRF-CEM cells. DNA fragmentation detection in breast adenocarcinoma MCF-7 cells showed that BSC triggered cell death is concentration and time dependent. We also show that two of these compounds, BSC 3g and 3n, cause cell-cycle arrest in the late G2/M in MCF-7 cells. Consistent with this, a reduction in CDK1 and CDK2 expression with no change in cyclin A an B1 was observed in this cell line. Activation of caspase-2 was also detected. However, the involvement of the caspase-dependent pathway in the process of cell death induced by either BSC 3g or 3n is discarded since cell death could not be prevented by pretreatment with the pancaspase inhibitor z-VAD-fmk. Moreover, since reduced levels of p21CIP1 and Chk2 proteins but no change in p53 levels could be detected in MCF-7 cells after BSC 3g or 3n treatment our results suggest that BSC treated cells die from lethal mitosis.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T2 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-N GENE-N GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
z-VAD-fmk Bisacylimidoselenocarbamates p53 CDK1 CDK2 cyclin A an B1 caspase-2 caspase caspase p21CIP1 Bisacylimidoselenocarbamate Chk2 CDK1 Chk2 BSC BSC phosphatidylserine BSC BSC BSC BSC BSC