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2017 ; 8
(16
): 27120-27136
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Gambogic acid suppresses cancer invasion and migration by inhibiting
TGF?1-induced epithelial-to-mesenchymal transition
#MMPMID28404892
Zhao K
; Zhang S
; Song X
; Yao Y
; Zhou Y
; You Q
; Guo Q
; Lu N
Oncotarget
2017[Apr]; 8
(16
): 27120-27136
PMID28404892
show ga
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.