title: 1-o-acetylbritannilactone (ABL) inhibits angiogenesis and lung cancer cell growth through regulating VEGF-Src-FAK signaling.
abstract: The search for safe, effective and affordable therapeutics against non-small cell lung cancer (NSCLC) and other lung cancers is important. Here we explored the potential effect of 1-o-acetylbritannilactone (ABL), a novel extract from Inula britannica-F, on angiogenesis and lung cancer cell growth. We demonstrated that ABL dose-dependently inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration, and capillary structure formation of cultured human umbilical vascular endothelial cells (HUVECs). In vivo, ABL administration suppressed VEGF-induced new vasculature formation in Matrigel plugs. For the mechanism investigations, we found that ABL largely inhibited VEGF-mediated activation of Src kinase and focal adhesion kinase (FAK) in HUVECs. Furthermore, treatment of A549 NSCLC cells with ABL resulted in cell growth inhibition and Src-FAK in-activation. Significantly, administration of a single dose of ABL (12 mg/kg/day) remarkably suppressed growth of A549 xenografts in nude mice. In vivo microvessels formation and Src activation were also significantly inhibited in ABL-treated xenograft tumors. Taken together, our findings suggest that ABL suppresses angiogenesis and lung cancer cell growth possibly via regulating the VEGFR-Src-FAK signaling.
authors.affiliation: Department of Thoracic Surgery, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Zhengfu
authors.affiliation: Department of Thoracic Surgery, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Huiwen
authors.affiliation: Department of Thoracic Surgery, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhijun
authors.affiliation: Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jiaojie
authors.affiliation: Zhejiang University School of Medicine, Hangzhou, China. Electronic address: xiaoyiyan163@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiaoyi
authors.affiliation: Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China. Electronic address: xiujuncaomaj@163.com.
authors.forename: Cai
authors.initials: C
authors.lastname: Xiujun
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D007783:Lactones; D042461:Vascular Endothelial Growth Factor A; C487680:acetylbritannilatone; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases
keywords: 1-o-acetylbritannilactone (ABL); Angiogenesis; Src-FAK and non-small cell lung cancers (NSCLC); VEGF