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Natural drugs in cancer treatment and their cytotoxicity
Hájková, Tereza ; Raudenská, Martina (referee) ; Provazník, Ivo (advisor)
The thesis deals with the natural substances in context with the cancer disease. The natural substances have a positive effect on the human organism and they are able to influence the viability and the growth of the cancer cells. The main mechanical device is to influence the mechanisms needed to start the apoptosis of the cancer cells and stopping further proliferation. The cancer cell lines utilization in the cancer disease is discussed in the thesis too. The thesis states common methods of determining the natural substances cytotoxicity. For the experimental part of the thesis it was chosen the MTT test method and the xCELLigence system for monitoring in real time. The mechanical device of the tested substance capsaicin in application on the prostate cell lines, tumorous PC3 and nontumorous PNT1A influence will be observed within the experimental part of the thesis.
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Molecular mechanism of anti-cancer activity of selected natural compounds.
Smolová, Dagmar ; Vališ, Karel (advisor) ; Flieger, Miroslav (referee)
Molecular mechanism of anti-cancer activity of selected natural compounds Přírodovědecká fakulta Univerzity Karlovi v Praze Smolová Dagmar Nowadays, cancer is affecting more then a third of the world's population and it's the cau- se of more than 20% of all deaths. A better understanding of cancer at the epigenic, gene- tic, molecular and cellular levels is opening up lots of opportunities to intervene with the goal of preventing end-stage of the invasive disease. Recently, much attention is paid to the natural substances because of its ability to interact specifically in the tumorgenesis. This compounds are preferred before the standard treatment because of its availability and safe- ty. In this work, there were observed the effects of 6-shogaol, 6-gingerol and galangin in the leukemic cells Jurkat. The greatest efficiency was showed by 6-shogaol wich caused apoptosis in cells by activating the antiproliferative signalling of Hippo pathway and it also decreased the expression of C-MYC oncogene. There was also a decline of C-MYC onco- protein wich has a key role in the tumor cells metabolism through it's ability to provide enought of energy for the growth and active proliferation. (In Czech)
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The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells.
Čermáková, Lucie ; Novotná, Eva (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Lucie Čermáková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells Leukemia presents malignant diseases of hematopoiesis, which essence is the malignant transformation of a hematopoietic stem cell at various levels of maturation and increased proliferative activity. Chemotherapy is the gold standard in the treatment of leukemia. One of the many treatments is the use of anthracycline chemotherapeutics, especially daunorubicin (DAU). Anthracyclines are widely used in clinical practice but have high cardiotoxic effects that limit their dosage. One of the main causes of side effects is the reduction of an anthracycline chemotherapeutic to the appropriate toxic metabolite, which accumulates in the heart. Carbonyl, reducing enzymes from the superfamily aldo-ketoreductase (AKR), and short-chain dehydrogenase/reductase (SDR) are involved in this reduction. At the same time, carbonyl reducing enzymes, has been shown to be involved in the mechanisms that cause tumor cells to be resistant to anthracyclines, thereby reducing the inhibition of the growth of these cells. In the diploma thesis we found that...
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Study of the mechanism of anticancer drug action on neuroblastomas
Černá, Tereza ; Stiborová, Marie (advisor) ; Souček, Pavel (referee) ; Mrízová, Iveta (referee)
Despite advances in cancer diagnosis and therapy, cancer is the second leading cause of death globally. The improvements of cancer treatment are the major challenge in this research. The aim of the thesis was studying of effects of two anticancer drugs ellipticine (Elli) and doxorubicin (DOX) on some cancer and healthy cell lines. Specific consideration was given to expand current knowledge about the metabolism and cytostatic effects of Elli in neuroblastoma cell lines. Another part of this study was focused on mechanisms contributing to the development of ellipticine-resistance in cancer cells and influence of histone deacetylase inhibitors on anticancer therapy was investigated. Moreover, the aim was to develop apoferritin (Apo) nanocarrier suitable for the active transport of cytostatics to cancer cells. Several essential data were found in this doctoral thesis. Anticancer efficiency of Elli depends on the CYP3A4-mediated metabolism in cancer. The CYP3A4 enzyme encapsulated into two nanoparticle forms, liposomes and SupersomesTM , was tested to activate ellipticine to its reactive species forming covalent DNA adducts. The formation of adducts seems to be dependent on concentrations of CYP3A4 in nanoparticle systems. A higher effectiveness of CYP3A4 in SupersomesTM than in liposomes to form...
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Molecular mechanism of anti-cancer activity of selected natural compounds.
Smolová, Dagmar ; Vališ, Karel (advisor) ; Flieger, Miroslav (referee)
Molecular mechanism of anti-cancer activity of selected natural compounds Přírodovědecká fakulta Univerzity Karlovi v Praze Smolová Dagmar Nowadays, cancer is affecting more then a third of the world's population and it's the cau- se of more than 20% of all deaths. A better understanding of cancer at the epigenic, gene- tic, molecular and cellular levels is opening up lots of opportunities to intervene with the goal of preventing end-stage of the invasive disease. Recently, much attention is paid to the natural substances because of its ability to interact specifically in the tumorgenesis. This compounds are preferred before the standard treatment because of its availability and safe- ty. In this work, there were observed the effects of 6-shogaol, 6-gingerol and galangin in the leukemic cells Jurkat. The greatest efficiency was showed by 6-shogaol wich caused apoptosis in cells by activating the antiproliferative signalling of Hippo pathway and it also decreased the expression of C-MYC oncogene. There was also a decline of C-MYC onco- protein wich has a key role in the tumor cells metabolism through it's ability to provide enought of energy for the growth and active proliferation. (In Czech)
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Impact of the regulatory T cells detection and differences in expession of tumor antigens in ovarian cancer
Kloudová, Kamila ; Sojka, Luděk (advisor) ; Čáp, Michal (referee)
Regulatory T cells (Treg) play a key role in maintaining the immune tolerance. They suppress development of autoimmune diseases and contribute to maintaining the homeostasis of the immune system. Expansion and excessive ability of regulatory T cells to suppress the immune response is increasingly observed also at many types of cancer. Due to the active inhibition of the antitumor immune response Treg contribute to tumor progression. Specific phenotype based detection and analysis of Treg functional properties may contribute to the successful monitoring of Treg accounts and to the effective cancer immunotherapy itself. Tumor cells express high amounts of so-called tumor antigens, which may play a key role in the antitumor immune response. Expression level of the tumor antigens gives the evidence about relevancy of each antigen in the specific immune response and efficiency of cancer immunotherapy. These data are obviously important to be obtained from the tumor cell lines as well as primary tumor cells. In the first part of the thesis I was focusing on the quantitative analysis of regulatory T cells in tumor tissue and peripheral blood of patients with ovarian cancer. For this purpose I used the newly introduced methyl-sensitive quantitative PCR (MS-qPCR) method and compare the data with the widely...
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Natural drugs in cancer treatment and their cytotoxicity
Hájková, Tereza ; Raudenská, Martina (referee) ; Provazník, Ivo (advisor)
The thesis deals with the natural substances in context with the cancer disease. The natural substances have a positive effect on the human organism and they are able to influence the viability and the growth of the cancer cells. The main mechanical device is to influence the mechanisms needed to start the apoptosis of the cancer cells and stopping further proliferation. The cancer cell lines utilization in the cancer disease is discussed in the thesis too. The thesis states common methods of determining the natural substances cytotoxicity. For the experimental part of the thesis it was chosen the MTT test method and the xCELLigence system for monitoring in real time. The mechanical device of the tested substance capsaicin in application on the prostate cell lines, tumorous PC3 and nontumorous PNT1A influence will be observed within the experimental part of the thesis.
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