Isolinderalactone Suppresses the Progression of Cholangiocarcinoma by Modulating the CARMA1-BCL10-MALT1 Signalosome

This interaction disrupted the formation of the CARMA1-BCL10-MALT1 (CBM) signalosome and consequently reduced BCL10 ubiquitination. Functional experiments confirmed this mechanism: BCL10 knockdown mimicked ILL's inhibitory effects, while a BCL10 mutation abolished them. Furthermore, activation of NF-κB with Diprovocim partially reversed ILL's suppressive effects.

In a xenograft nude mouse model, ILL effectively reduced tumor growth without significant toxicity and suppressed NF-κB activation in tumor tissues. These findings demonstrate that Isolinderalactone suppresses CCA progression by modulating the CBM signalosome and BCL10 ubiquitination to regulate the NF-κB pathway, supporting its potential as a promising therapeutic candidate for CCA.