Biological Evaluation of a New Brassinosteroid: Antiproliferative Effects and Targeting Estrogen Receptor α Pathways. Issue 9 (3rd September 2019)

• Record Type: Journal Article
• Authors: Scherbakov, Alexander M.; Zhabinskii, Vladimir N.; Khripach, Vladimir A.; Shcherbinin, Dmitrii S.; Mekhtiev, Arif R.; Shchegolev, Yuri Yu.; Savochka, Aleh P.; Andreeva, Olga E.
• Is Part Of: Chemistry & biodiversity. Volume 16:Issue 9(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-09-03
• Subjects: brassinosteroids -- breast cancer -- estrogen receptor α -- AP-1 -- survivin; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.201900332
• Languages: English
• ISSNs: 1612-1872

Abstract

Abstract: 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. Abstract :