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Cancer Cell International
Published in: Cancer Cell International 1/2015

Open Access 01-12-2015 | Primary research

The role of individual caspases in cell death induction by taxanes in breast cancer cells

Authors: Michael Jelínek, Kamila Balušíková, Martina Schmiedlová, Vlasta Němcová-Fürstová, Jan Šrámek, Jitka Stančíková, Ilaria Zanardi, Iwao Ojima, Jan Kovář

Published in: Cancer Cell International | Issue 1/2015

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Abstract

Background

In previous study we showed that caspase-2 plays the role of an apical caspase in cell death induction by taxanes in breast cancer cells. This study deals with the role of other caspases. We tested breast cancer cell lines SK-BR-3 (functional caspase-3) and MCF-7 (nonfunctional caspase-3).

Methods and results

Using western blot analysis we demonstrated the activation of initiator caspase-8 and -9 as well as executioner caspase-6 and -7 in both tested cell lines after application of taxanes (paclitaxel, SB-T-1216) at death-inducing concentrations. Caspase-3 activation was also found in SK-BR-3 cells. Employing specific siRNAs after taxane application, suppression of caspase-3 expression significantly increased the number of surviving SK-BR-3 cells. Inhibition of caspase-7 expression also increased the number of surviving SK-BR-3 and MCF-7 cells. On the other hand, suppression of caspase-8 and caspase-9 expression had no significant effect on cell survival. However, caspase-9 seemed to be involved in the activation of caspase-3 and caspase-7. Caspase-3 and caspase-7 appeared to activate mutually. Furthermore, we observed a significant decrease in mitochondrial membrane potential (flow cytometric analysis) and cytochrome c release (confocal microscopy, western blot after cell fractionation) from mitochondria in SK-BR-3 cells. No such changes were observed in MCF-7 cells after taxane treatment.

Conclusion

We conclude that the activation of apical caspase-2 results in the activation of caspase-3 and -7 without the involvement of mitochondria. Caspase-9 can be activated directly via caspase-2 or alternatively after cytochrome c release from mitochondria. Subsequently, caspase-9 activation can also lead to caspase-3 and -7 activations. Caspase-3 and caspase-7 activate mutually. It seems that there is also a parallel pathway involving mitochondria that can cooperate in taxane-induced cell death in breast cancer cells.
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Metadata
Title
The role of individual caspases in cell death induction by taxanes in breast cancer cells
Authors
Michael Jelínek
Kamila Balušíková
Martina Schmiedlová
Vlasta Němcová-Fürstová
Jan Šrámek
Jitka Stančíková
Ilaria Zanardi
Iwao Ojima
Jan Kovář
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-015-0155-7

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