Metaphase arrest and cell death induced by etoposide on HeLa cells.
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 microM etoposide (incubation for only 3h) 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).
Rello-Varona
Santiago
S
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, C/ Darwin 2, Citología A-115, E-28049 Madrid, Spain.
Gámez
Angelo
A
Moreno
Vanessa
V
Stockert
Juan Carlos
JC
Cristóbal
Javier
J
Pacheco
María
M
Cañete
Magdalena
M
Juarranz
Angeles
A
Villanueva
Angeles
A
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology* / Q000633:toxicity; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D011123:Polyploidy; D008941:Spindle Apparatus / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide