Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells

Iranzu      Lamberto; Daniel      Plano; Esther      Moreno; Maria      Font; Juan      Antonio Palop; Carmen      Sanmartin; Ignacio      Encio

doi:10.2174/0929867311320120010

Abstract

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.

Keywords: Bisacylimidoselenocarbamates, CDK1, Chk2, G2/M cell cycle arrest, MCF-7 breast cancer cells

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