title: alpha-Tocopheryl succinate inhibits angiogenesis by disrupting paracrine FGF2 signalling.
abstract: Malignant mesothelioma (MM) cells enhanced proliferation of endothelial cells (ECs) as well as their angiogenesis in vitro by secretion of fibroblast growth factor-2 (FGF2). This effect was suppressed by pre-treating MM cells with alpha-tocopheryl succinate (alpha-TOS), which inhibited FGF2 secretion by inducing mitochondria-dependent generation of reactive oxygen species. The role of FGF2 was confirmed by its down-regulation by treating MM cells with siRNA, abolishing EC proliferation and wound healing enhancement afforded by MM cells. We conclude that alpha-TOS disrupts angiogenesis mediated by MM cells by inhibiting FGF2 paracrine signalling.
authors.affiliation: Apoptosis Research Group, Heart Foundation Research Centre, School of Medical Science, Griffith Institute of Health and Medical Research, Griffith University, Southport 4222, Qld, Australia. j.neuzil@griffith.edu.au
authors.forename: Jiri
authors.initials: J
authors.lastname: Neuzil
authors.forename: Emma
authors.initials: E
authors.lastname: Swettenham
authors.forename: Xiu-Fang
authors.initials: XF
authors.lastname: Wang
authors.forename: Lan-Feng
authors.initials: LF
authors.lastname: Dong
authors.forename: Michael
authors.initials: M
authors.lastname: Stapelberg
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D008654:Mesothelioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology