Faculty of Pharmacy, Lj. (FFALJ)
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Chemo-sensitizing effects of EP4 receptor-inducedinactivation of nuclear factor-$▫kappaB▫$Gobec, Martina, farmacevtka, 1983- ...The EP4 receptor conveys growth-inhibitory effects in mature and immature B cells via NF-kB. Herein, the EP4 receptor was evaluated as a potential therapeutic target for leukemia and lymphoma, whose ... survival depends on the constitutive activity of NF-ŽB. Utilizing a pharmacological approach, we proved that the EP4 receptor induces caspase-mediated apoptosis in malignantly transformed B cells, with the most prominent effect being on Burkitt's lymphoma cells. Since the increased activation of NF-kB underlies multi-drug resistance phenomena, we modulated this signaling pathway via EP4 receptor triggering. Pge1-OH, a specific EP4 receptor agonist, led to decreased NF-kB activity and a consequent decrease in levels of the antiapoptotic gene Bcl-xL in Ramos cells, resulting in an elevated sensitivity of cells towards bortezomib- and doxorubicin-induced chemotherapeutic effects. Our study identifies the as yet unrecognized potential of EP4 receptor agonists as chemo-sensitizing agents in B-cell lymphoma. The specific downregulation of NF-kB-dependent pathways in B-cell malignancies opens new possibilities for treatment and current therapy optimization using specific EP4 receptor agonists.Source: European Journal of Pharmacology. - ISSN 0014-2999 (Vol. 742, Nov. 2014, str. 81-88)Type of material - article, component partPublish date - 2014Language - englishCOBISS.SI-ID - 3734897
Author
Gobec, Martina, farmacevtka, 1983- |
Prijatelj, Matevž |
Delič, Jozo |
Markovič, Tijana
Other authors
Mlinarič-Raščan, Irena
Topics
EP4 receptor |
leukemia |
apoptosis |
chemosenzitation |
NF-[kappa]B
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Gobec, Martina, farmacevtka, 1983- | 32034 |
Prijatelj, Matevž | 29602 |
Delič, Jozo | ![]() |
Markovič, Tijana | 34223 |
Mlinarič-Raščan, Irena | 12443 |
Source: Personal bibliographies
and: SICRIS
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