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Sample-based modeling reveals bidirectional interplay between cell cycle progression and extrinsic apoptosis.

Dirke Imig1, Nadine Pollak2,3, Frank Allgöwer1,3

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Cell cycle progression significantly impacts extrinsic apoptosis. TRAIL-induced apoptosis is faster in G1 phase, suggesting G1 enrichment can improve TRAIL-based cancer treatments.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Apoptotic cell death is initiated via extrinsic and intrinsic pathways.
  • Cell cycle progression influences intrinsic apoptosis, but its role in extrinsic apoptosis is less understood.

Purpose of the Study:

  • To investigate the cell cycle dependency of TRAIL-induced extrinsic apoptosis.
  • To analyze the interaction between cell death timing and cell cycle progression.

Main Methods:

  • Utilized fluorescence-based time-lapse microscopy for monitoring cell cycle and apoptosis.
  • Employed sampling-based mathematical modeling for quantitative analysis.
  • Conducted experiments on NCI-H460/geminin and HCT-116 cell lines.

Main Results:

  • TRAIL exposure prolongs cell cycle progression.
  • Cells treated with TRAIL in G1 phase exhibit faster apoptosis kinetics compared to those in S/G2/M.
  • Mathematical modeling indicated decelerated apoptosis progression in the latter half of the cell cycle.

Conclusions:

  • Cell cycle progression and extrinsic apoptosis are interdependent.
  • Enriching cell populations in G1 phase may reduce resistance to TRAIL-induced apoptosis.
  • Findings offer insights for optimizing TRAIL-based therapeutic strategies.