The novel brassinosteroid analog BR4848 inhibits angiogenesis in human endothelial cells and induces apoptosis in human cancer cells in vitro
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F18%3A73592325" target="_blank" >RIV/61989592:15110/18:73592325 - isvavai.cz</a>
Alternative codes found
RIV/61389030:_____/18:00489630 RIV/68378050:_____/18:00489630 RIV/61989592:15310/18:73592325
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0960076018300062" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0960076018300062</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jsbmb.2018.01.005" target="_blank" >10.1016/j.jsbmb.2018.01.005</a>
Alternative languages
Result language
angličtina
Original language name
The novel brassinosteroid analog BR4848 inhibits angiogenesis in human endothelial cells and induces apoptosis in human cancer cells in vitro
Original language description
We report the synthesis and detailed biological study of the synthetic brassinosteroid analog 2 alpha,3 alpha-dihydroxy-6-oxo-5 alpha-androstan-17 beta-yl N-(tert-butoxycarbonyl)-D,L-valinate (BR4848). The panel of cancer cell lines was used for characterization of its antiproliferative activity, yet had no adverse effects in normal human fibroblasts. In HeLa cells, BR4848-induced apoptosis was accompanied by increase of apoptotic subG(1) cells, PARP-1 and caspase-7 fragmentation, downregulation of Bcl-2 and Mcl-1, an increase in caspase activity and G(2)/M phase cell cycle arrest. Antiproliferative properties of BR4848 were exhibited by inhibition of phosphorylation of Akt, Erk1/2 and FAK. Furthermore, the developed analog exhibited in vitro antiangiogenic activity in human umbilical vein endothelial cells (HUVECs). BR4848-induced apoptosis accompanied with G2/M arrest was detected in endothelial cells. BR4848 also inhibited adhesion, tube formation and migration of endothelial cells by inhibition of FAY, Erk 1/2, CDK5, VEGFR2, TNF alpha-stimulated production of IL-6, angiopoietin-2 and Jagged1. Finally, BR4848 did not modulate the activity nor nuclear translocation of any of the steroid receptors (ER alpha, ER beta, AR, MR and PR) included in reporter cell-based assays, which excludes the genomic activity of steroid receptors as a contributing factor to the observed biological activities of BR4848.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
ISSN
0960-0760
e-ISSN
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Volume of the periodical
178
Issue of the periodical within the volume
APR
Country of publishing house
GB - UNITED KINGDOM
Number of pages
9
Pages from-to
263-271
UT code for WoS article
000428483800030
EID of the result in the Scopus database
2-s2.0-85040446184