title: Vitamin E analogues inhibit angiogenesis by selective induction of apoptosis in proliferating endothelial cells: the role of oxidative stress.
abstract: "Mitocans" from the vitamin E group of selective anticancer drugs, alpha-tocopheryl succinate (alpha-TOS) and its ether analogue alpha-TEA, triggered apoptosis in proliferating but not arrested endothelial cells. Angiogenic endothelial cells exposed to the vitamin E analogues, unlike their arrested counterparts, readily accumulated reactive oxygen species (ROS) by interfering with the mitochondrial redox chain and activating the intrinsic apoptotic pathway. The vitamin E analogues inhibited angiogenesis in vitro as assessed using the "wound-healing" and "tube-forming" models. Endothelial cells deficient in mitochondrial DNA (mtDNA) were resistant to the vitamin E analogues, both in ROS accumulation and apoptosis induction, maintaining their angiogenic potential. alpha-TOS inhibited angiogenesis in a mouse cancer model, as documented by ultrasound imaging. We conclude that vitamin E analogues selectively kill angiogenic endothelial cells, suppressing tumor growth, which has intriguing clinical implications.
authors: Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Queensland, Australia.
authors: Lan-Feng
authors: LF
authors: Dong
authors: Emma
authors: E
authors: Swettenham
authors: Johanna
authors: J
authors: Eliasson
authors: Xiu-Fang
authors: XF
authors: Wang
authors: Mikhal
authors: M
authors: Gold
authors: Yasmine
authors: Y
authors: Medunic
authors: Marina
authors: M
authors: Stantic
authors: Pauline
authors: P
authors: Low
authors: Lubomir
authors: L
authors: Prochazka
authors: Paul K
authors: PK
authors: Witting
authors: Jaroslav
authors: J
authors: Turanek
authors: Emmanuel T
authors: ET
authors: Akporiaye
authors: Stephen J
authors: SJ
authors: Ralph
authors: Jiri
authors: J
authors: Neuzil
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D004351:Drug Resistance; D004730:Endothelium, Vascular; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D014810:Vitamin E