Title:Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells
VOLUME: 20 ISSUE: 12
Author(s):Iranzu Lamberto, Daniel Plano, Esther Moreno, Maria Font, Juan Antonio Palop, Carmen Sanmartin and Ignacio Encio
Affiliation:Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain.
Keywords:Bisacylimidoselenocarbamates, CDK1, Chk2, G2/M cell cycle arrest, MCF-7 breast cancer cells
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.
