α-Tocopheryl succinate inhibits angiogenesis by disrupting paracrine FGF2 signalling

FEBS Letters. 2007 Oct 2;581(24):4611-5. Epub 2007 Aug 31. [Link]

Neuzil J, Swettenham E, Wang XF, Dong LF, Stapelberg M.

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

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 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.

Keywords: α-Tocopheryl succinate, FGF2, Endothelial cell, Angiogenesis, Paracrine signalling

Abbreviations:

• DCF: dihydrodichlorofluorescein diacetate
• EC: endothelial cell
• FGF2: fibroblast growth factor-2
• MM: malignant mesothelioma
• NS: non-silencing
• RNAi: RNA interference
• ROS: reactive oxygen species
• siRNA: short interfering RNA
• α-TOS: α-tocopheryl succinate
• VE: vitamin E