Dokument: Griseofulvin inhibiert das Wachstum der Nebennierenrindenkarzinom-Zelllinie NCI-H295R in vitro
| Titel: | Griseofulvin inhibiert das Wachstum der Nebennierenrindenkarzinom-Zelllinie NCI-H295R in vitro | |||||||
| Weiterer Titel: | Griseofulvin inhibits the growth of adrenocortical cancer cells in vitro | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=48219 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20190109-084053-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Bramann, Eva Louise [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Klöcker, Nikolaj [Gutachter] Prof. Dr. Willenberg, Holger S. [Gutachter] | |||||||
| Stichwörter: | Griseofulvin, Nebenierenkarzinom, NCI H295-R | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Das Adrenokortikale Karzinom (ACC) ist ein seltener, maligner endokriner Tumor mit einer schlechten Prognose. Histopathologisch finden sich im Adrenokortikalen Karzinom häufig atypische Mitosen mit erhöhter Spindelanzahl.
Diese atypischen Mitosen stellen ein Risiko für Krebszellen dar, da sie zu einer Teilung in mehr als zwei Zellen führen und Chromosomen ungleichmäßig verteilt werden. Dies kann in nicht lebensfähigen Tochterzellen resultieren. Atypische Mitosen können durch eine zentrosomale Amplifikation verursacht sein. Das Zentrosomale Clustering ist ein Mechanismus, den eine betroffene Tumorzelle entwickeln kann, um überzählige Zentrosomen zu zwei Spindelpolen zusammen zufassen und so ihre genetische Integrität zu schützen. Griseofulvin – ein bereits bekanntes Antimykotikum – blockiert diesen Mechanismus. Ob Griseofulvin wachstumshemmend auf adrenokortikalen Zellen wirkt, ist bislang nicht bekannt. Vor diesem Hintergrund untersuchten wir die Effekte von Griseofulvin in der ACC-Zelllinie NCI-H295R hinsichtlich von Wachstums- und Stoffwechseleigenschaften mittels Water-soluble-tetrazoliumsalt-1-Assay (Wst-1-Assay), Bromdesoxyuridin-Assay (BrdUrd-Assay) und [³H]-Thymidin Assay. Die Apoptoserate wurde durch einen Caspase 3/7-Assay und Lichtmikroskopie bestimmt. Nach 24 h Inkubation mit Griseofulvin konnte eine dosisabhängige Hemmung der Proliferation auf bis zu 57 %, sowie eine Reduktion der Stoffwechselaktivität auf bis zu 69 % im Vergleich mit der unbehandelten Kontrolle gemessen werden. Lichtmikroskopisch ergab sich das typische Bild apoptotischer Zellen. Im Caspase-Assay konnte eine dosisabhängige Steigerung der Caspase-Aktivität um 425 % im Vergleich zur unbehandelten Kontrolle nachgewiesen werden. In der Zusammenschau stellen Griseofulvin oder seine Derivate einen interessanten Ansatz für die Therapieforschung beim ACC dar.Adrenocortical cancer is a rare, malignant tumor with a poor prognosis. It is often associated with atypical mitoses and supernumerary spindles. Atypical mitoses represent a risk to cancer cells as they can lead up to a division into more than two cells and unevenly distributed chromosomes. This may result in non-viable daughter cells. Atypical mitoses can be caused by centrosomal clustering. Centrosomal clustering is a mechanism used by cancer cells with supernumerary centrosomes to solve the threatening problem of multipolar spindles. Griseofulvin is an antifungal substance that interferes with the microtubule apparatus and inhibits centrosomal clustering. It has also been demonstrated that griseofulvin inhibits the growth of tumor cells in vitro and in vivo. However, it is not yet known whether treatment with griseofulvin inhibits growth of adrenocortical tumor cells. We studied the viability and antiproliferative effects of griseofulvin on cultured NCI-H295R adrenocortical carcinoma cells using Wst-1-, BrdUrd- and [3H]-thymidine assays. For the detection of apoptosis we used a caspase 3/7 cleavage assay and light microscopy techniques. We observed that incubation with griseofulvin for 24 – 48 h leads to a decrease in the viability and proliferation of NCI-H295R cells in a dose-dependent manner. Significant effects could be observed after incubation with griseofulvin as measured by Wst-1-, BrdUrd-, and [3H] dT- uptake assays. Apoptosis of NCI-H295R cells was increased in a dose-dependent manner up to 4.5- fold after incubation with griseofulvin 40 M for 24 h as shown by caspase 3/7 cleavage assay and light microscopy. With regard to new treatment strategies for adrenocortical cancer, griseofulvin, and possibly other agents, which interfere with the microtubule apparatus and inhibit centrosomal clustering, may turn out to be interesting targets for further research. | |||||||
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| Rechtliche Vermerke: | Ich versichere an Eides statt, dass diese Dissertation selbständig und ohne unzulässige fremde Hilfe erstellt worden ist und die hier vorgelegte Dissertation nicht von einer anderen medizinischen Fakultät abgelehnt worden ist. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 9/2009 - 5/2018 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 09.01.2019 | |||||||
| Dateien geändert am: | 09.01.2019 | |||||||
| Promotionsantrag am: | 05.07.2017 | |||||||
| Datum der Promotion: | 15.05.2018 |
