1. Synthetic E-guggulsterone derivative GSD-1 inhibits NF-κB signaling and suppresses the metastatic potential of breast cancer cells.
- Author
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Abdellatef AA, Zhou Y, Yamada A, Elmekkawy SA, Kohyama A, Yokoyama S, Meselhy MR, Matsuya Y, Sakurai H, and Hayakawa Y
- Subjects
- Animals, Breast Neoplasms pathology, Cell Line, Tumor, Humans, Mice, Signal Transduction drug effects, Tumor Necrosis Factor-alpha pharmacology, Wound Healing drug effects, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, NF-kappa B antagonists & inhibitors, Pregnenediones pharmacology
- Abstract
Guggulsterone (GS) [4,17(20)-pregnadiene-3,16-dione], is the main active phytosterol constituent in guggul, the gum resin of Commiphora wightii (Arnott.) Bhand./Commiphora mukul Engl. tree, and is known for its medicinal effects. In this study, we report that GSD-1, a structurally-related synthetic GS derivative, strongly inhibits NF-κB activation induced by TNF-α. GSD-1 prevented the nuclear translocation of p65 through the blockade of IκBα degradation and p65 phosphorylation, and further inhibited the activation of upstream kinases, including transforming growth factor-β activated kinase 1 (TAK1), IκB kinase (IKK) α, and IKKβ. Furthermore, GSD-1 inhibited the cell-intrinsic activation of NF-κB, and exerted its direct anti-cancer and anti-metastatic effects in both murine and human breast cancer cell lines. This study demonstrated GSD-1 to be an attractive compound to target NF-κB activation that has potential for treating breast cancer growth and metastasis., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2021
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