The role of individual caspases in cell death induction by taxanes in breast cancer cells
Autor: | Martina Schmiedlová, Kamila Balušíková, Jan Kovář, Jitka Stancikova, Vlasta Němcová-Fürstová, Ilaria Zanardi, Michael Jelinek, Jan Šrámek, Iwao Ojima |
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Jazyk: | angličtina |
Předmět: |
Cell death
Programmed cell death Cancer Research Mitochondrion Bioinformatics Taxanes 03 medical and health sciences chemistry.chemical_compound Breast cancer 0302 clinical medicine Western blot Genetics Medicine Caspase 030304 developmental biology 0303 health sciences biology medicine.diagnostic_test business.industry Cytochrome c Cell biology Paclitaxel chemistry Oncology Cell culture Caspases 030220 oncology & carcinogenesis biology.protein Cell fractionation Primary Research business |
Zdroj: | Cancer Cell International |
ISSN: | 1475-2867 |
DOI: | 10.1186/s12935-015-0155-7 |
Popis: | 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. |
Databáze: | OpenAIRE |
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