Estrogen-Like Effect of Mitotane Explained by Its Agonist Activity on Estrogen Receptor-α.

ABSTRACT: Mitotane is the cornerstone of medical treatment of adrenocortical carcinoma. Estrogenic-like side effects frequently occur in patients, and previous studies explored the chemical nature of the interaction between estrogen receptor-α (ER-α) and toxic compounds, including the DDD derivatives. We used molecular docking and molecular dynamics (MD) simulations to explore the possible interaction between mitotane and the ER-α receptor and the induced conformational changes. The ER-α expressing MCF-7 cells were exposed to mitotane with/without tamoxifen, and the cell viability/proliferation was evaluated by MTT assay and direct count. The transient ER-α silencing was performed using two ER-α siRNA (50 nM) and verified by Western blot. MDA-MB-231 cells were used as a negative control. Mitotane sh

SUBMITTER: Rossini E 

PROVIDER: S-EPMC8235434 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature