APPLICATION OF NEW ORGANOMETALLIC COMPOUNDS ON OVARIAN CANCER CELL LINES

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F17%3A00097633" target="_blank" >RIV/00216224:14310/17:00097633 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

APPLICATION OF NEW ORGANOMETALLIC COMPOUNDS ON OVARIAN CANCER CELL LINES

Popis výsledku v původním jazyce

The synthesis of compounds with the central metal atom in its structure represents very up-todate and attractive trend in anticancer drug development programmes. The first such compound is a cisplatin, whose cytotoxic effects were discovered in 1967 by Barnett Rosenberg (1). In spite of the indisputable success against some types of human malignancies, cisplatin as well as its derivatives displays a number of side effects such as nephrotoxicity, haemolytic anemia and other. Important problems are also toxicity towards normal fast dividing cells and progression of drug resistance during the therapy (2). The limitations of cisplatin started research focused on other transition metal complexes different from platinum, e.g. Fe, Ru, Ti, Zr, etc., which as we believe may in near future substitute cisplatin-based antitumor therapy. In collaboration with several laboratories a series of new organometallic complexes containing iron in their structure was synthesised. The cytotoxicity of these compounds was then monitored on selected ovarian cancer cell lines A2780, A2780cis and SK-OV-3 (3, 4, unpublished data). Compounds with the highest cytotoxic effect have been chosen to study their ability to cumulate inside the cells. We developed a new method based on differential pulse voltammetry (DPV), to determine the amount of accumulated drugs. These data were compared with the results obtained from ICP-MS, which is ordinarily used to detect metals at very low concentrations. Both methods confirmed elevated levels of iron in tested cancer cells (4, unpublished data). Based on this, DPV was used to determine the processes responsible for cellular uptake of selected compounds more in detail. Another important goal is to find out the mechanism by which ferrocenes operate in a cancer cells. Our preliminary experiments indicate an increased development of oxygen radicals that may represent a key cytotoxic mechanism of action induced by these drugs.

Název v anglickém jazyce

APPLICATION OF NEW ORGANOMETALLIC COMPOUNDS ON OVARIAN CANCER CELL LINES

Popis výsledku anglicky

The synthesis of compounds with the central metal atom in its structure represents very up-todate and attractive trend in anticancer drug development programmes. The first such compound is a cisplatin, whose cytotoxic effects were discovered in 1967 by Barnett Rosenberg (1). In spite of the indisputable success against some types of human malignancies, cisplatin as well as its derivatives displays a number of side effects such as nephrotoxicity, haemolytic anemia and other. Important problems are also toxicity towards normal fast dividing cells and progression of drug resistance during the therapy (2). The limitations of cisplatin started research focused on other transition metal complexes different from platinum, e.g. Fe, Ru, Ti, Zr, etc., which as we believe may in near future substitute cisplatin-based antitumor therapy. In collaboration with several laboratories a series of new organometallic complexes containing iron in their structure was synthesised. The cytotoxicity of these compounds was then monitored on selected ovarian cancer cell lines A2780, A2780cis and SK-OV-3 (3, 4, unpublished data). Compounds with the highest cytotoxic effect have been chosen to study their ability to cumulate inside the cells. We developed a new method based on differential pulse voltammetry (DPV), to determine the amount of accumulated drugs. These data were compared with the results obtained from ICP-MS, which is ordinarily used to detect metals at very low concentrations. Both methods confirmed elevated levels of iron in tested cancer cells (4, unpublished data). Based on this, DPV was used to determine the processes responsible for cellular uptake of selected compounds more in detail. Another important goal is to find out the mechanism by which ferrocenes operate in a cancer cells. Our preliminary experiments indicate an increased development of oxygen radicals that may represent a key cytotoxic mechanism of action induced by these drugs.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10600 - Biological sciences

Projekt

<a href="/cs/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů