Vitamin E analogues inhibit angiogenesis by selective induction of apoptosis in proliferating endothelial cells: the role of oxidative stress
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Swettenham, Emma
Eliasson, Johanna
Wang, Xiu-Fang
Gold, Mikhal
Medunic, Yasmine
Stantic, Marina
Low, Pauline
Prochazka, Lubomir
Witting, Paul K
Turanek, Jaroslav
Akporiaye, Emmanuel T
Ralph, Stephen J
Neuzil, Jiri
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Abstract
''Mitocans'' from the vitamin E group of selective anticancer drugs, A-tocopheryl succinate (A-TOS) and its ether analogue A-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 ''woundhealing'' 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. A-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.
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Cancer Research
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67
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24
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© 2007 ASPET. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the author for more information.
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Oncology and carcinogenesis
Biochemistry and cell biology