Gambogic acid suppresses cancer invasion and migration by inhibiting TGF?1-induced epithelial-to-mesenchymal transition.

ABSTRACT: The epithelial-to-mesenchymal transition (EMT) contributes to the disruption of cell-cell junctions and imbues cancer cells with invasive and migratory properties. In this study, we investigated the effect of gambogic acid, a xanthone extracted from the resin of Garciania hanburyi, on transforming growth factor ?1 (TGF?1)-induced EMT. Gambogic acid inhibited the invasion and migration of TGF?1-induced A549 cells in vitro. Gambogic acid also increased the mRNA and protein expression of E-cadherin, but repressed the mRNA and protein expression of N-cadherin, vimentin, and transcription factor TWIST1. Further examination of the mechanism revealed that the nuclear factor ?B (NF-?B) pathway is involved in this regulation of EMT-related biomarkers. Gambogic acid inhibited NF-?B p65 nuclear translocation and the phosphorylation of the inhibitor of NF-?B (I?B?) and I?B? kinase (IKK?). Gambogic acid also suppressed the EMT induced by TGF?1 and tumor necrosis factor ? by inhibiting the NF-?B pathway. Our data also indicate that gambogic acid inhibited the primary lesion and lung metastasis of orthotopic model of A549 cells in vivo. We propose that gambogic acid might be developed as a candidate drug with therapeutic potential for the treatment of cancer invasion and migration.

SUBMITTER: Zhao K 

PROVIDER: S-EPMC5432322 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature