The role of individual caspases in cell death induction by taxanes in breast cancer cells.
The role of individual caspases in cell death induction by taxanes in breast cancer cells.
复制标题
DOI：
10.1186/s12935-015-0155-7
复制
发表时间：
2015
影响因子：
5.8
通讯作者：
Kovář J
中科院分区：
文献类型：
--
作者：
Jelínek M;Balušíková K;Schmiedlová M;Němcová-Fürstová V;Šrámek J;Stančíková J;Zanardi I;Ojima I;Kovář J
在前期的研究中我们发现caspase-2在紫杉烷诱导乳腺癌细胞死亡中起着顶端caspase的作用。本研究涉及其他半胱天冬酶的作用。我们测试了乳腺癌细胞系SK-BR-3（功能性caspase-3）和MCF-7（非功能性caspase-3）。使用蛋白质印迹分析，我们证明了在应用死亡诱导浓度的紫杉烷（紫杉醇，SB-T-1216）后，在两种测试的细胞系中引发剂半胱天冬酶-8和-9以及执行剂半胱天冬酶-6和-7的活化。SK-BR-3细胞中也发现Caspase-3活化。在紫杉烷应用后使用特异性siRNA，抑制caspase-3表达显著增加了存活的SK-BR-3细胞的数量。caspase-7表达的抑制也增加了存活的SK-BR-3和MCF-7细胞的数量。另一方面，抑制caspase-8和caspase-9的表达对细胞存活没有显著影响。然而，caspase-9似乎参与了caspase-3和caspase-7的激活。caspase-3和caspase-7相互激活。此外，我们观察到SK-BR-3细胞中线粒体膜电位（流式细胞术分析）和细胞色素c释放（共聚焦显微镜，细胞分级分离后的蛋白质印迹）显著降低。紫杉烷处理后MCF-7细胞中未观察到这种变化。我们的结论是，顶端的caspase-2的激活导致caspase-3和-7的激活，而不涉及线粒体。半胱天冬酶-9可以直接通过半胱天冬酶-2激活，或者在细胞色素c从线粒体释放后激活。随后，半胱天冬酶-9活化也可导致半胱天冬酶-3和-7活化。caspase-3和caspase-7相互激活。似乎还有一个涉及线粒体的平行途径，可以在紫杉烷诱导的乳腺癌细胞死亡中合作。
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). 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. 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.
登录
查看更多内容
影响因子：
--
作者：
Brentnall M;Rodriguez-Menocal L;De Guevara RL;Cepero E;Boise LH
通讯作者：
Boise LH
影响因子：
3.4
作者：
Musílková, J;Kovár, J
通讯作者：
Kovár, J
影响因子：
7.2
作者：
Koc, M;Nad'ová, Z;Kovár, J
通讯作者：
Kovár, J
影响因子：
5.2
作者：
Drago-Ferrante, Rosa;Santulli, Andrea;Vento, Renza
通讯作者：
Vento, Renza
影响因子：
5.6
作者：
Fabbri, Francesco;Amadori, Dino;Silvestrini, Rosella
通讯作者：
Silvestrini, Rosella