Medizinische Universität Graz - Research portal
Selected Publication:
Jantscher, S.
Investigating the function of agents possessing lymphoma suppressive properties.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2022.
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- Authors Med Uni Graz:
- Advisor:
- Deutsch Alexander
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- Abstract:
- The non-Hodgkin Lymphoma (NHL) is considered the most common hematological malignancy worldwide. The incidence of the aggressive subtype DLBCL is steadily increasing. As preliminary data already show cell proliferation inhibitory effects of two compounds, Brusatol and F3AK, we will further examine their in vitro effects in aggressive lymphomas. We used different human lymphoma cell lines: representing DLBCL-GCB models, DLBCL-ABC models, Burkitt’s lymphoma model and a model for T-cell NHL. Those cells were treated with Brusatol or F3AK, followed by cell cycle analysis (PI staining) and apoptosis assays (Annexin V staining, cleavage of caspase 3, and via Western blot PARP cleavage was assessed). G0/G1 cell cycle arrest was induced by treatment with Brusatol or F3AK, and apoptotic effects were also observed. A poorer response of the ABC-DLBCL cell line was noted for both substances. Gene expression analysis by Western blot and qPCR showed down-regulation of the pro-apoptotic gene p53 as well as the anti-apoptotic genes BCL-XL and MCL-1 at mRNA and protein level. The data indicate that Brusatol and F3AK induce cell growth inhibition mediated by G0/G1 cell cycle arrest in aggressive lymphoma cells, promote apoptosis and lead to down-regulation of anti-apoptotic genes and p53. These compounds could serve as novel therapeutic therapies. Since Nr4a1 influences tumorigenesis and apoptosis via cytochrome c release, my research group investigated the effects of Nr4a1 agonists Csn-B, c10i and C-DIM in the mouse cell setting. We used an EµMyc Nr4a1 +/+ and EµMyc Nr4a1 -/- murine lymphoma cell line and treated them with these Nr4a1 agonists. A qPCR was carried out to perform gene expression. Treatment with Csn-B and c10i strongly dose-dependently induced Nr4a1 expression in Nr4a1-proficient lymphoma cells already after 1h treatment compared to DMSO control. Our findings suggest that Nr4a1 acts as a regulator of specific immune checkpoints.