9-Bromonoscapine-induced mitotic arrest of cigarette smoke condensate-transformed breast epithelial cells

Aruna S. Jaiswal, Ritu Aneja, Shahnjayla K. Connors, Harish C. Joshi, Asha S. Multani, Sen Pathak, Satya Narayan

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1146-1156
Number of pages11
JournalJournal of Cellular Biochemistry
Volume106
Issue number6
DOIs
StatePublished - Apr 15 2009
Externally publishedYes

Keywords

  • 9-bromonoscapine
  • Apoptosis
  • Breast cancer
  • Cell cycle
  • Cigarette smoke condensate
  • Mitotic arrest

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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