alpha-Tocopheryl succinate inhibits angiogenesis by disrupting paracrine FGF2 signalling.
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.
Neuzil
Jiri
J
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
Swettenham
Emma
E
Wang
Xiu-Fang
XF
Dong
Lan-Feng
LF
Stapelberg
Michael
M
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