α-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 α-tocopheryl succinate (α-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 α-TOS disrupts angiogenesis mediated by MM cells by inhibiting FGF2 paracrine signalling.