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Biological Evaluation of a New Brassinosteroid: Antiproliferative Effects and Targeting Estrogen Receptor α Pathways
Author(s) -
Scherbakov Alexander M.,
Zhabinskii Vladimir N.,
Khripach Vladimir A.,
Shcherbinin Dmitrii S.,
Mekhtiev Arif R.,
Shchegolev Yuri Yu.,
Savochka Aleh P.,
Andreeva Olga E.
Publication year - 2019
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201900332
Subject(s) - transactivation , brassinosteroid , chemistry , estrogen receptor , survivin , receptor , cancer research , transcription factor , breast cancer , biochemistry , apoptosis , biology , cancer , gene , arabidopsis , genetics , mutant
Brassinosteroids (BS), a class of plant‐specific steroid hormones, are considered as new potential anticancer agents for the treatment of tumors of different origin, including hormone‐dependent cancers. Effects of a synthetic brassinosteroid BS4 ((22 R ,23 R ,24 R )‐22,23‐dihydroxy‐24‐methyl‐B‐homo‐7‐oxa‐5 α ‐cholest‐2‐en‐6‐one ((3a S ,7a R ,7b S ,9a S ,10 R ,12a S ,12b S )‐10‐[(2 S ,3 R ,4 R ,5 R )‐3,4‐dihydroxy‐5,6‐dimethylheptan‐2‐yl]‐7a,9a‐dimethyl‐1,3a,4,7,7a,7b,8,9,9a,10,11,12,12a,12b‐tetradecahydro‐3 H ‐benzo[ c ]indeno[5,4‐ e ]oxepin‐3‐one)) on hormone‐dependent breast cancer cells and normal epithelial cells and its impact on the estrogen receptor signaling were evaluated. Cytotoxicity was assessed by MTT‐test; expression of estrogen receptor α and survivin was measured by immunoblotting. Transactivation analysis of luciferase reporter gene was performed for ER α and AP‐1 factors after the brassinosteroid treatment. Dock6 and Autodock Vina were used for molecular docking. BS4 revealed a significant antiproliferative effect towards the hormone‐dependent breast cancer cells and was not active against normal epithelial cells. BS4 action on MCF‐7 breast cancer cells was found to be complex: a decrease in ER α expression as well as in its transcription activity was accompanied by inhibition of ER α ‐related signaling pathways (AP‐1 complex and survivin). BS4 binding mode to ER α ligand‐binding domain was analyzed by molecular docking. The obtained results show that antiproliferative and antiestrogenic properties of the brassinosteroid BS4 , as well as its ability to inhibit the anti‐apoptotic protein survivin may be of interest for further development of anticancer agents.