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The role of caspase 2 in apoptosis induction in tumor cells.
Schmiedlová, Martina ; Kovář, Jan (advisor) ; Horníková, Lenka (referee)
Within the cell, caspase-2 probably fulfills several functions. Caspase-2 can be involved in apoptosis induction, DNA repair as well as cell cycle regulation. Caspase-2 has the character of initiator and also executioner caspase. A stimulus for caspase 2 activation can be oxidative stress or DNA damage. Caspase-2 is activated by cleavadge during an interaction with protein complexes. One of protein complexes,i.e. PIDDosome, is made of protein PIDD, RAIDD and pro-caspase-2. Withine the PIDDosome, caspase-2 is activated. Activated caspase-2 occures in a short S form and in long L form. L form of caspase-2 has proapoptotic effects and S form of caspase-2 has antiapoptotic effects. Caspase-2S has been only detected on mRNA level but not on protein level. The main role of caspase-2L is apoptosis induction in normal and tumor cells. Caspase-2 in tumour cells is activated by extrinstic as well as intristic apoptotic pathway. Apoptosis induction by caspase-2 is for example studied in connection with breast cancer treatment with taxanes. Caspase-2 ability of apoptosis induction in cancer cells independently of p53 protein is employed in cancer treatment including overcoming the resistance to apoptosis induction which is based on loosing p53 activity. Caspase-2 is involved in apoptosis induction by different...
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Role of the mitochondrial pathway in apoptosis induction by taxanes in breast cancer cells
Schmiedlová, Martina ; Kovář, Jan (advisor) ; Anděra, Ladislav (referee)
Apoptosis represents one of the cell death mechanisms which is realized after the application of taxanes in breast cancer cell lines. Apoptosis induction can be principally triggered either by outer or inner pathway. The aim of the diploma thesis is to contribute to the elucidation of role and mechanisms of the inner mitochondrial pathway of apoptosis induction after taxane application (paclitaxel and SB-T-1216) employing a model of breast carcinoma cell lines SK- BR-3 (nonfunctional p53, functional capase-3) and MCF-7 (functional p53, nonfunctional caspase-3). Specifically, we tested the effect of both employed taxanes on mitochondrial membrane potential, ROS level and the expression and localization of proteins regulating inner mitochondrial pathway. Taxane application resulted in mitochondrial membrane dissipation in SK-BR-3 cell line. However, this was not shown in MCF-7 cell line. We found no changes in Bax and Smac/DIABLO expression after taxane application in both tested cell lines. There was a decrease of Bid expression after taxane application in SK-BR-3 line, but not in MCF-7 line. Taxane application did not lead to the translocation of Bax and Bid (tBid) proteins from cytosol to mitochondria in both tested cell lines. Similarly, there was no Smac/DIABLO release from mitochondria to...
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Role of the mitochondrial pathway in apoptosis induction by taxanes in breast cancer cells
Schmiedlová, Martina ; Kovář, Jan (advisor) ; Anděra, Ladislav (referee)
Apoptosis represents one of the cell death mechanisms which is realized after the application of taxanes in breast cancer cell lines. Apoptosis induction can be principally triggered either by outer or inner pathway. The aim of the diploma thesis is to contribute to the elucidation of role and mechanisms of the inner mitochondrial pathway of apoptosis induction after taxane application (paclitaxel and SB-T-1216) employing a model of breast carcinoma cell lines SK- BR-3 (nonfunctional p53, functional capase-3) and MCF-7 (functional p53, nonfunctional caspase-3). Specifically, we tested the effect of both employed taxanes on mitochondrial membrane potential, ROS level and the expression and localization of proteins regulating inner mitochondrial pathway. Taxane application resulted in mitochondrial membrane dissipation in SK-BR-3 cell line. However, this was not shown in MCF-7 cell line. We found no changes in Bax and Smac/DIABLO expression after taxane application in both tested cell lines. There was a decrease of Bid expression after taxane application in SK-BR-3 line, but not in MCF-7 line. Taxane application did not lead to the translocation of Bax and Bid (tBid) proteins from cytosol to mitochondria in both tested cell lines. Similarly, there was no Smac/DIABLO release from mitochondria to...
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The role of caspase 2 in apoptosis induction in tumor cells.
Schmiedlová, Martina ; Horníková, Lenka (referee) ; Kovář, Jan (advisor)
Within the cell, caspase-2 probably fulfills several functions. Caspase-2 can be involved in apoptosis induction, DNA repair as well as cell cycle regulation. Caspase-2 has the character of initiator and also executioner caspase. A stimulus for caspase 2 activation can be oxidative stress or DNA damage. Caspase-2 is activated by cleavadge during an interaction with protein complexes. One of protein complexes,i.e. PIDDosome, is made of protein PIDD, RAIDD and pro-caspase-2. Withine the PIDDosome, caspase-2 is activated. Activated caspase-2 occures in a short S form and in long L form. L form of caspase-2 has proapoptotic effects and S form of caspase-2 has antiapoptotic effects. Caspase-2S has been only detected on mRNA level but not on protein level. The main role of caspase-2L is apoptosis induction in normal and tumor cells. Caspase-2 in tumour cells is activated by extrinstic as well as intristic apoptotic pathway. Apoptosis induction by caspase-2 is for example studied in connection with breast cancer treatment with taxanes. Caspase-2 ability of apoptosis induction in cancer cells independently of p53 protein is employed in cancer treatment including overcoming the resistance to apoptosis induction which is based on loosing p53 activity. Caspase-2 is involved in apoptosis induction by different...
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