Influence of salinomycin treatment on division and movement of individual cancer cells cultured in normoxia or hypoxia evaluated with time-lapse digital holographic microscopy

Cell Cycle. 2017;16(21):2128-2138. doi: 10.1080/15384101.2017.1380131. Epub 2017 Oct 4.

Abstract

Most studies on new cancer drugs are based on population-derived data, where the absence of response of a small population may pass unnoticed. Thus, individual longitudinal tracking of cells is important for the future development of efficient cancer treatments. We have used digital holographic microscopy to track individual JIMT-1 human breast cancer cells and L929 mouse fibroblast cultivated in normoxia or hypoxia. In addition, JIMT-1 cells were treated with salinomycin, a cancer stem cell targeting compound. Three-day time-lapse movies were captured and individual cells were analysed with respect to cell division (cell cycle length) and cell movement. Comparing population-doubling time derived from population-based growth curves and individual cell cycle time data from time-lapse movies show that the former hide a sub-population of dividing cells. Salinomycin treatment increased the motility of cells, however, this motility did not result in an increased distant migration i.e. the cells increased their local movement. MCF-7 breast cancer cells showed similar motility behaviour as salinomycin-treated JIMT-1 cells. We suggest that combining features, such as motility and migration, can be used to distinguish cancer cells with mesenchymal (JIMT-1) and epithelial (MCF-7) features. The data clearly emphasize the importance of longitudinal cell tracking to understand the biology of individual cells under different conditions.

Keywords: Digital holography; cell cycle; cell migration; hypoxia; longitudinal tracking of individual cells; normoxia; salinomycin; time-lapse.

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Hypoxia / metabolism*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Pyrans / pharmacology*

Substances

  • Pyrans
  • salinomycin