title: Gambogic acid suppresses cancer invasion and migration by inhibiting TGFβ1-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 β1 (TGFβ1)-induced EMT. Gambogic acid inhibited the invasion and migration of TGFβ1-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 κB (NF-κB) pathway is involved in this regulation of EMT-related biomarkers. Gambogic acid inhibited NF-κB p65 nuclear translocation and the phosphorylation of the inhibitor of NF-κB (IκBα) and IκBα kinase (IKKα). Gambogic acid also suppressed the EMT induced by TGFβ1 and tumor necrosis factor α by inhibiting the NF-κB 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.
authors.affiliation: State Key Laboratory of Natural Medicines, College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Chia Tai Tianqing Pharmaceutical Group Co., Ltd, People's Republic of China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural Medicines, College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Natural Medicines, College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicines, College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
authors.affiliation: State Key Laboratory of Natural Medicines, College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D012333:RNA, Messenger; D051785:Smad Proteins; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C052659:gambogic acid
keywords: A549 cells; EMT; NF-κB; gambogic acid; invasion