Akademik Veri Yönetim Sistemi
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, cilt.254, 2025 (SCI-Expanded)
Elucidating the mechanisms of action of natural metabolites may be promising in the emergence of alternative candidate therapeutics. In the present study, the combined approaches of in silico molecular docking (MD) and in vitro analyses were conducted to investigate the interacting partners of 24-epibrassinolide (EBR) as a steroidderived phytohormone in cancer cells and evaluate the cell death mechanisms associated with these partners. EBR scoring functions were initially calculated against the selected 35 functional target proteins, which may interact with steroids, for tumor biology using AutoDock Tools-1.5.7 receptor-ligand MD software. Molecular analyses were carried out in breast, pancreatic, and hepatocellular carcinoma cell lines. Our results showed that the retinoic acid nuclear receptor gamma (RAR gamma) was the most stable interacting partner with a binding energy (BE). Furthermore, the secondary simulation analyses obtained the lowest BE score for EBR among RAR gamma selective agonistic compounds. According to our data, EBR was significantly inhibited the cell viability of MDA-MB-231, MIA-PaCa-2, and Hep-G2 cells, and diminished the colony formation potential. We showed that RAR gamma was inhibited after increasing concentration of EBR, by affecting the downstream target's expressions including p21, p16, p27, p57 and cyclin D1 detected by qRT-PCR. We also investigated the effect of EBR treatment on the expression levels of the proteins linked to nuclear hormone receptor (NHR) expressions, apoptosis, endoplasmic reticulum stress, and Hippo-Yes-associated protein (YAP)/ Transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathways. Our findings indicated that EBR is a strong ER stress modulator, apoptosis inducer in a caspase-dependent manner, and effector for the modulation of Hippo-YAP-TAZ signaling pathways through the interaction with retinoic acid receptor.