|
| |
|
| |
|
|
The study of the influence of vitamin E analogues on malignant mesothelioma
Kovářová, Jaromíra ; Neužil, Jiří (advisor) ; Kozubík, Alois (referee) ; Vítek, Libor (referee)
Cancer is a leading cause of death in the western world and is increasing in frequency world-wide. Although diagnosis, treatment and therapeutic approaches to cancer have improved, many types of cancer are still lethal due to the lack of radical treatment. One of the fatal neoplastic disease types with poor prognosis is represented by malignant mesothelioma (MM). MM is characterised by very high mortality rate and limited therapeutic options. The etiology of the disease is mainly associated with exposure to asbestos fibres. The incidence of MM is increasing in many countries. The search for novel molecular targets, anti-cancer strategies and drugs, which would considerably improve the treatment is of great importance. Certain new drugs, especially those with specific molecular targets, show high selectivity in their action to cancer cells, and have considerably increased the cure rate in some types of cancer. Mitochondria have recently emerged as a very promising target for anti-cancer agents. A group of compounds with anti-cancer activity that induce apoptosis by way of mitochondrial destabilisation, termed 'mitocans', have been a recent focus of research. Several mitocans have been shown to selectively induce apoptosis in cancer cells and suppress the growth of many types of carcinomas in...
|
|
|
Role of signaling pathways and redox processes in cancer cell biology
Vališ, Karel ; Kovář, Jan (advisor) ; Anděra, Ladislav (referee) ; Kozubík, Alois (referee)
5 identifikovali VDAC2 protein jako možný transportér železa do nádorových buněk a tudíž možný cíl protinádorové terapie. Abstract Specific apoptosis induction in cancer cells represents promising way of anticancer therapy without damaging healthy tissues. Hence, search for new molecular targets capable of specific apoptosis triggering is highly challenging, mainly due to new and effective anti-cancer therapies development. Cancer cell metabolism (1) and mainly mitochondrial metabolism (2) seems to represent intriguing target. Mitochondria play essential role in life of the cell but on the other hand mitochondria activate cell death which is usually connected to increased ROS (reactive oxygen species) production. Contribution of this work is identification of vitamin E analogues as inhibitors of complex II and potent inductors of mitochondrial ROS in cancer cells. Additionally, we have demonstrated activation of conserved Hippo/Mst1 kinase in response to the vitamin E analogues which results in FoxO1 nuclear localization, NOXA gene transactivation, Bak protein activation, mitochondrial membrane permeabilisation and apoptosis induction. Next we searched for membrane proteins with increased expression in cancer cells exposed to iron deprivation. These proteins can play a role in iron metabolism of cancer...
|
|
| |
|
|
Polyunsaturated fatty acids (PUFAs) enhance the sensitivity of HT-29 human colon adenocarcinoma cell line to apoptotic effects of butyrate, anti-Fas and TNF-alpha
Vaculová, Alena ; Hofmanová, Jiřina ; Kovaříková, Martina ; Souček, Karel ; Šimek, V. ; Zadák, Z. ; Kozubík, Alois
Práce vede k závěrům, že vysoce nenasycené mastné kyseliny (pufas) zvyšují citlivost buněčné línie lidského adenokarcinomu kolonu ht-29 k apoptickým účinkům butyrátu, anti-fas a tnf-alpha
|
|
| |
|
| |
|
| |
|
| |
guest ::
