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The effect of trans-nerolidol and valencene in ovarian cancer cells
Zajdlová, Martina ; Skálová, Lenka (advisor) ; Králová, Věra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Martina Zajdlová Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The effect of trans-nerolidol and valencene in ovarian cancer cells Trans-nerolidol and valencene belong to sesquiterpenes, which present a large group of secondary plant metabolites. In practice, we can encounter them in the food or perfume industry. However, they are also used in traditional Chinese medicine. Recently, the biological activities of sesquiterpenes, which include e.g. anti-inflammatory or antineoplastic activities, were studied. Doxorubicin is one of the most important cytostatic drugs and various ways to improve its effectiveness and reduce side effects are being studied. One such usage is in combination therapy with natural substances, e.g. with sesquiterpenes. The aim of this study was to test antiproliferative effects of doxorubicin, trans-nerolidol and valencene on ovarian cancer cell lines SK-OV-3 and A2780. We also assayed the possible pro-oxidant potential of doxorubicin and terpenes by measuring the production of ROS. In addition, we evaluated the interaction between doxorubicin and terpenes by quantification of combination indexes. We also studied the possible effect of...
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Sesquiterpenes in cancer therapy
Ambrož, Martin ; Skálová, Lenka (advisor) ; Hodek, Petr (referee) ; Souček, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Martin Ambrož Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Title of Doctoral Thesis: Sesquiterpenes in cancer therapy. Chemotherapy is an important part of treatment of cancer. Currently, the use of several anticancer drugs in combination seem to be more advantageous. This combination therapy prevents drug resistance development and make it possible to lower the doses of single drugs, which prevents the side effects in non-cancerous tissues. Large pool of potential drugs for combination therapy can be found among natural compounds, for example among sesquiterpenes. Our project was designed to evaluate the effect of Myrica rubra essential oil (MEO) and selected sesquiterpenes in combination cancer therapy. We focused on the potential ability of MEO and sesquiterpenes to increase the antiproliferative efficacy of classical cytostatics (doxorubicin, oxaliplatin, 5-fluorouracil). In addition, we also studied the possible interaction of sesquiterpenes with other drugs in combination therapy, which could be caused by sesquiterpene-mediated modulation of drug-metabolizing enzymes. For these purposes, a panel of various cell lines (both cancerous and non-cancerous) and primary culture of hepatocytes...
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The effect of humulene and caryophyllene oxide on the efficacy of 5-fluorouracil in colon cancer cells
Šadibolová, Michaela ; Skálová, Lenka (advisor) ; Králová, Věra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Michaela Šadibolová Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The effect of humulene and caryophyllene oxide on the efficacy of 5-fluorouracil in colon cancer cells 5-Fluorouracil (5-FU) represents a standard chemotherapeutic agent used in the treatment of several types of cancer diseases including the treatment of colorectal cancer. However, the clinical use of 5-FU is limited due to frequent chemoresistance of tumour cells. Sesquiterpenes are plant secondary metabolites that form a major part of plant essential oils. They have been found to possess a considerable antitumour activity and the ability to enhance the efficacy of some traditional chemotherapeutic agents. The aim of this study was to find out whether sesquiterpenes α-humulene (HUM) and caryophyllene oxide (CAO) influence the antiproliferative effect of 5-FU in human colorectal adenocarcinoma cell lines Caco-2 and SW-620 and to test the effect of 5-FU, CAO and their combination on the activity of initiator caspases 8 and 9 and effector caspase 3/7 in Caco-2 cell line. CAO showed strong antiproliferative effect in both cancer cell lines whereas HUM showed minimal effect on cell proliferation. In...
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The effect of nerolidol nad valencene on the efficacy of 5-fluorouracil in colon cancer cells
Pospíšilová, Eva ; Skálová, Lenka (advisor) ; Hanušová, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Eva Pospíšilová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The effect of nerolidol nad valencene on the efficacy of 5- fluorouracil in colon cancer cells The cancer diseases belong among the most serious diseases on the world. Cytostatics, which are used for treatment, have many side effects and there is a high occurrence of resistance. Therefore scientists are looking for appropriate substances for the combination therapy. Sesquiterpenes, secondary metabolites of plants, could be one of the options. The aims of this work were to study the influence of cytostatic 5-fluorouracil and two sesquiterpenes, nerolidol and valencene on the proliferation of intestinal cancer cells and to find out the influence of sesquiterpenes on antiproliferative effect of 5-fluorouracil. Cancer cell line SW-620 derived from the colorectal metastatic carcinoma was used for our experiments. Neutral red uptake tests were used to measure the number of viable cells. The obtained results showed, that the inhibition of proliferation of cells SW-620 by 5-fluorouracil was concentration and time dependent. Trans-nerolidol showed antiproliferative effect even in low concentrations, while valencene...
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The effect of nerolidol and farnesol on the selected hepatic biotransformation enzymes
Dimunová, Diana ; Skálová, Lenka (advisor) ; Boušová, Iva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Diana Dimunová Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The effect of nerolidol and farnesol on the selected hepatic biotransformation enzymes Sesquiterpenes represent a class of terpenoids that are mostly produced as secondary metabolites in higher plants. These compounds play an important role as components of many folk medicines and dietary supplements. In recent years, they have been studied in view of their antioxidant, anti-parasitic and anti-carcinogenic activities. On the other hand, sesquiterpenes could change the activity of biotransformation enzymes and by this way affect the metabolism of drugs, the safety and efficiency of pharmacotherapy. The aim of diploma thesis was to find out the influence of three acyclic sesquiterpenes farnesol (FAR), cis- nerolidol (CNER) and trans-nerolidol (TNER) on activity and expresion of reducing enzymes (aldehyd reductase AKR1A1, carbonyl reductase CBR1, NADH-quinone oxidoreductase1 NQO1) and conjugating enzymes (sulfotransferase SULT, glutathione-S-transferase GST, UDP-glucuronosyltransferase UGT). The potential inhibitory effects of sesquiterpenes were tested in hepatic subcellular fractions, while primary...
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Effect of prenylflavonoids on detoxification enzymes in hepatocytes
Štěpánková, Jana ; Szotáková, Barbora (advisor) ; Skálová, Lenka (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Jana Štěpánková Supervisor: Prof. Ing. Barbora Szotáková, Ph.D. Title of Diploma Thesis: The effect of prenylflavonoids on detoxifying enzymes in hepatocytes Prenylated flavonoids are secondary metabolites of many plants, for example hops and fig. They affect the human organism in many positive ways, for example they have antioxidazing, anticancer, anti-inflammatory, estrogenic and antibacterial effects. These effects are even more emphasized due to their prenylated group. Only dietary supplements have sufficient amount of these substances and that is the main reason of patients' purchase. Cytotoxicity of prenylated flavonoids xanthohumol (XH), isoxanthohumol (IXH), 6- prenylnaringenin (6PN) and 8-prenylnaringenin (8PN) towards isolated rat hepatocytes by using the MTT test was studied in this diploma thesis. Furthermore the influence of these prenylflavonoids on the activity and expression of phase I. biotransformation enzymes NAD(P)H:chinonoxidoreductase (NQO1) and aldehydreductase (AKR1A1) was examined. The results of the MTT viability test showed that 6PN and 8PN raise the viability of rat hepatocytes. The viability of hepatocytes was increased by 25 μM XH, however higher...
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The impact of selected prenylflavonoids on the effect of anticancer therapy in cancer cell lines
Pešková, Klára ; Matoušková, Petra (advisor) ; Skálová, Lenka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Klára Pešková Supervisor: Ing. Petra Matoušková, Ph.D. Title of diploma thesis: The impact of selected prenylflavonoids on the effect of anticancer therapy in cancer cell lines Prenylflavonoids 6-prenylnaringenin and 8-prenylnaringenin and flavonoid naringenin are substances with anti-proliferative properties. Prenylflavonoids are present mostly in hop and in beer. Main source of naringenin are primarily citrus fruits. In this diploma thesis the effect of compounds was tested by neutral red uptake test in cell lines SW480 and SW620. These substances were tested individually and then in combination with cytostatic agent oxaliplatin. Oxaliplatin is used in treatment of cancer disease. 6-prenylnaringenin was the most effective compound in both cell lines. Statistical evaluation of the effect was carried out by Graphpad using the method One-way ANOVA in comparison with control. Combination index was determined by software program Compusyn using the method by Chou-Talalay.
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The effect of sesquiterpenes on the hepatic cytochromes P450
Myslivečková, Zuzana ; Skálová, Lenka (advisor) ; Schröterová, Ladislava (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Zuzana Myslivečková Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Influence of selected sesquiterpenes on the activity of hepatic cytochromes P450 Sesquiterpenes are 15-carbon compounds that consist of 3 isoprenoid units in their molecule. Sesquiterpenes together with monoterpenes are the main components of plain essential oils and they play an important role in the plant development, physiology and ecological interactions. They are widely used in folk medicine and as a part of food supplements because of their biological effects - especially anti-inflammatory, anti-parasitic and anti-cancer. Moreover, essential oils represent a rich reservoir of candidate compounds, which could be potentially used as a drugs in future. The aim of the present study was to test and compare the influence of seven selected sesquiterpenes (β-caryophyllene, caryophyllene oxide, α-humulene, farnesole, valencene, trans-nerolidole and cis-nerolidole) on the activities of the main hepatic enzymes involved in phase I biotransformation of xenobiotics, cytochromes P450 (CYPs) 1A and 3A, in rat and human in in vitro model systems. In the present study, the activities of the CYP1A were assayed using...
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The effect of humulene, caryophyllene and caryophylllene oxide on the selected hepatic biotransformation enzymes
Nguyen, Thuy Linh ; Skálová, Lenka (advisor) ; Szotáková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Thuy Linh Nguyen Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The effect of humulene, caryophyllene and caryophyllene oxide on the activity of selected liver biotransformation enzymes Sesquiterpenes, secondary metabolites of higher plants, are formed from three isoprenoid units. They possess interesting biological activities, e.g. antibacterial, antimalarial or anticarcinogenic activities, however they could also influence the activity and/or the expression of biotransformation enzymes. The aim of this diploma thesis was to evaluate the effect of α-humulene (HUM), β-caryophyllene (CAR) and β-caryophyllene oxide (CAO) on the activity and expression of enzymes of phase I and II of xenobiotics biotransformation. In the first study, the potential inhibitory effect of HUM, CAO and CAR on the activity of selected enzymes in subcellular fractions obtained from rat liver homogenates was studied. In the second study, HUM, CAO and CAR were incubated with primary cultures of rat hepatocytes for 24 hours to determine the impact of sesquiterpenes on the viability of hepatocytes and potential modulatory effects of HUM, CAO, CAR on the activity and expression of selected...
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New analogs of anorexigenic neuropeptides involved in food intake regulation
Pražienková, Veronika ; Maletínská, Lenka (advisor) ; Novotný, Jiří (referee) ; Skálová, Lenka (referee)
This work focuses on anorexigenic neuropeptides, cocaine- and amphetamine-regulated transcript (CART) and prolactin-releasing peptide (PrRP), which decrease food intake and body weight. CART peptide is an anorexigenic neuropeptide and, despite many efforts, its receptor has not yet been identified. We found CART peptide specific binding sites in pheochromocytoma PC12 cells. Cells differentiated to neurons increased significantly the number of binding sites. On the other hand, after differentiation to chromaffin cells the number of binding sites was so low that it was impossible to determine their density. To clarify the importance of each of the three disulfide bridges in the CART molecule, analogs with one or two disulfide bridges were synthetized. The biological activity was maintained in analog with two disulfide bridges in positions 74-94 and 88-101. Moreover, we demonstrated the stimulation of JNK and subsequently c-Jun activation in PC12 cells. Neuropeptide PrRP belongs to the RF-amide peptide family and has anorexigenic properties. PrPR has a high affinity to GPR10 and neuropeptide FF (NPFF2) receptor. In our laboratory lipidized analogs of PrRP were synthesized, which are able to decrease food intake after peripheral administration and may cross the blood-brain barrier. We tested biological...
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