American Association for Cancer Research, Cancer Research, 24(67), p. 11906-11913, 2007
DOI: 10.1158/0008-5472.can-07-3034
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Abstract “Mitocans” from the vitamin E group of selective anticancer drugs, α-tocopheryl succinate (α-TOS) and its ether analogue α-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. α-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. [Cancer Res 2007;67(24):11906–13]