Synthetic E-guggulsterone derivative GSD-1 inhibits NF-κB signaling and suppresses the metastatic potential of breast cancer cells.

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.

• Authors: Amira A Abdellatef, Yue Zhou, Akane Yamada, Sahar A Elmekkawy, Aki Kohyama, Satoru Yokoyama, Meselhy R Meselhy, Yuji Matsuya, Hiroaki Sakurai, Yoshihiro Hayakawa
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 140 Pg. 111737 (Aug 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34020249 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antineoplastic Agents
• NF-kappa B
• Pregnenediones
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Humans
• Mice
• NF-kappa B (antagonists & inhibitors)
• Pregnenediones (pharmacology)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (pharmacology)
• Wound Healing (drug effects)