Metaphase arrest and cell death induced by etoposide on HeLa cells

• Published in: The international journal of biochemistry & cell biology 2006, Vol.38 (12), p.2183-2195
• Main Authors: Rello-Varona, Santiago, Gámez, Angelo, Moreno, Vanessa, Stockert, Juan Carlos, Cristóbal, Javier, Pacheco, María, Cañete, Magdalena, Juarranz, Ángeles, Villanueva, Ángeles
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Cell Death - drug effects; Cell Survival - drug effects; Etoposide; Etoposide - pharmacology; Etoposide - toxicity; Flow Cytometry; HeLa Cells; Humans; Metaphase - drug effects; Metaphase arrest; Microscopy, Electron, Scanning; Mitotic catastrophe; Polyploidy; Spindle Apparatus - drug effects
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2006.06.013

DNA damage, cell cycle and apoptosis form a network with important implications for cancer chemotherapy. Dysfunctions of the cycle checkpoints can allow cancer cells to acquire drug resistance. Etoposide is a well-known inducer of apoptosis, which is widely used in cell biology and in clinical practice. In this work we report that a pulse of 50 μM etoposide (incubation for only 3 h) on HeLa cells causes a sequence of events that leads to abnormal mitotic figures that could be followed either by cell death or, more commonly, by interphase restitution and endocycle. The endocycling polyploid cells enter immediately into mitosis and suffer metaphase blockage with multiple spindle poles, which were generally followed by a direct triggering of apoptosis from metaphase (mitotic catastrophe), or by a new process of endocycling, until surviving cells finally became apoptotic (96 h after the treatment).