title: Bisacylimidoselenocarbamates cause G2/M arrest associated with the modulation of CDK1 and Chk2 in human breast cancer MCF-7 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 p21(CIP1) 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.
authors: Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain.
authors: Iranzu
authors: I
authors: Lamberto
authors: Daniel
authors: D
authors: Plano
authors: Esther
authors: E
authors: Moreno
authors: María
authors: M
authors: Font
authors: Juan Antonio
authors: JA
authors: Palop
authors: Carmen
authors: C
authors: Sanmartín
authors: Ignacio
authors: I
authors: Encío
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D064447:Checkpoint Kinase 2; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D016566:Organoselenium Compounds; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D020169:Caspases