Transgenerational cell fate profiling: a method for the graphical presentation of complex cell cycle alterations.

Abstract

The illicit generation of tetraploid cells constitutes a prominent driver of oncogenesis, as it often precedes the development of aneuploidy and genomic instability. In addition, tetraploid (pre-)malignant cells display an elevated resistance against radio- and chemotherapy. Here, we report a strategy to preferentially kill tetraploid tumor cells based on the broad-spectrum kinase inhibitor SP600125. Live videomicroscopy revealed that SP600125 affects the execution of mitosis, impedes proper cell division and/or activates apoptosis in near-to-tetraploid, though less so in parental, cancer cells. We propose a novel graphical model to quantify the differential response of diploid and tetraploid cells to mitotic perturbators, including SP600125, which we baptized "transgenerational cell fate profiling." We speculate that this representation constitutes a valid alternative to classical "single-cell fate" and "genealogical" profiling and, hence, may facilitate the analysis of cell fate within a heterogeneous population as well as the visual examination of cell cycle alterations.

• Authors: Mohamed Jemaà, Lorenzo Galluzzi, Oliver Kepp, Maria Castedo, Santiago Rello-Varona, Ilio Vitale, Guido Kroemer
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 12 Issue 1 Pg. 183-90 (Jan 01 2013) ISSN: 1551-4005 [Electronic] United States
• PMID: 23255111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Protein Kinase Inhibitors
• Tumor Suppressor Protein p53
• pyrazolanthrone

Topics

• Anthracenes (toxicity)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Diploidy
• HCT116 Cells
• Humans
• Microscopy, Video
• Protein Kinase Inhibitors (toxicity)
• Tetraploidy
• Tumor Suppressor Protein p53 (deficiency, genetics, metabolism)