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
Current Medicinal Chemistry
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:
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.
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Lamberto Iranzu, Plano Daniel, Moreno Esther, Font Maria, Antonio Palop Juan, Sanmartin Carmen and Encio Ignacio, Bisacylimidoselenocarbamates Cause G2/M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF-7 Cells, Current Medicinal Chemistry 2013; 20 (12) . https://dx.doi.org/10.2174/0929867311320120010
DOI https://dx.doi.org/10.2174/0929867311320120010 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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