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

Citation:
Synthetic E-guggulsterone derivative GSD-1 inhibits NF-κB signaling and suppresses the metastatic potential of breast cancer cells., Abdellatef, Amira A., Zhou Yue, Yamada Akane, Elmekkawy Sahar A., Kohyama Aki, Yokoyama Satoru, Meselhy Meselhy R., Matsuya Yuji, Sakurai Hiroaki, and Hayakawa Yoshihiro , Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Volume 140, p.111737, (2021)

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.