9‐bromonoscapine‐induced mitotic arrest of cigarette smoke condensate‐transformed breast epithelial cells
- 19 February 2009
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 106 (6), 1146-1156
- https://doi.org/10.1002/jcb.22099
Abstract
In the present investigation, we determined the chemotherapeutic efficacy of 9‐bromonoscapine (Br‐Nos), a more potent noscapine analog, on MCF10A, spontaneously immortalized human normal breast epithelial cells and MCF10A‐CSC3, cigarette smoke condensate (CSC)‐transformed cells. The results from cytogenetic analysis showed that Br‐Nos induced polyploidy and telomeric association in MCF10A‐CSC3 cells, while MCF10A cells remained unaffected. Our immunofluorescence data further demonstrated that MCF10A‐CSC3 cells were susceptible to mitotic catastrophe on exposure to Br‐Nos and failed to recover after drug withdrawal. MCF10A‐CSC3 cells exhibited Br‐Nos‐induced aberrant multipolar spindle formation, which irreversibly impaired the alignment of replicated chromosome to the equatorial plane and finally culminated in cell death. Although MCF10A cells upon Br‐Nos treatment showed bipolar spindles with some uncongressed chromosomes, these cells recovered fairly well after drug withdrawal. Our flow‐cytometry analysis data reconfirmed that MCF10A‐CSC3 cells were more susceptible to cell death compared to MCF10A cells. Furthermore, our results suggest that decreased levels of cdc2/cyclin B1 and cdc2 kinase activity are responsible for Br‐Nos‐induced mitotic cell arrest leading to cell death in MCF10A‐CSC3 cells. This study thus explores the underlying mechanism of Br‐Nos‐induced mitotic catastrophe in CSC‐transformed MCF10A‐CSC3 cells and its potential usefulness as a chemotherapeutic agent for prevention of cigarette smoke‐induced breast cancer growth. J. Cell. Biochem. 106: 1146–1156, 2009.Keywords
This publication has 54 references indexed in Scilit:
- Structure/Function Analysis of the Interaction of Adenomatous Polyposis Coli with DNA Polymerase β and Its Implications for Base Excision RepairBiochemistry, 2007
- p53 and p21 Determine the Sensitivity of Noscapine-Induced Apoptosis in Colon Cancer CellsCancer Research, 2007
- Cigarette smoke condensate-induced level of adenomatous polyposis coli blocks long-patch base excision repair in breast epithelial cellsOncogene, 2006
- Mitotic Checkpoint Slippage in Humans Occurs via Cyclin B Destruction in the Presence of an Active CheckpointCurrent Biology, 2006
- Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cellsJournal of Cellular Biochemistry, 2004
- Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitroOncogene, 2004
- Chromosome-Microtubule Interactions During MitosisAnnual Review of Cell and Developmental Biology, 2002
- Telomeric protein Pin2/TRF1 induces mitotic entry and apoptosis in cells with short telomeres and is down-regulated in human breast tumorsOncogene, 2001
- CDC2 Activation Is Not Required for Thymocyte ApoptosisBiochemical and Biophysical Research Communications, 1994
- p21 is a universal inhibitor of cyclin kinasesNature, 1993