1. Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress
- Author
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Paul K. Witting, Emma Swettenham, Yasmine Medunic, Jiri Neuzil, Lubomir Prochazka, Lan-Feng Dong, Mikhal Gold, Jaroslav Turánek, Johanna Eliasson, Emmanuel T. Akporiaye, Stephen John Ralph, Pauline Low, Marina Stantic, and Xiu-Fang Wang
- Subjects
Cancer Research ,Programmed cell death ,Endothelium ,Angiogenesis ,medicine.medical_treatment ,Drug Resistance ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Apoptosis ,Biology ,medicine.disease_cause ,DNA, Mitochondrial ,medicine ,Humans ,Vitamin E ,Neovascularization, Pathologic ,Cell growth ,Mitochondria ,Endothelial stem cell ,Oxidative Stress ,medicine.anatomical_structure ,Oncology ,Biochemistry ,Cancer research ,Endothelium, Vascular ,Oxidative stress - 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]
- Published
- 2007
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