期刊
REDOX REPORT
卷 19, 期 1, 页码 16-25出版社
MANEY PUBLISHING
DOI: 10.1179/1351000213Y.0000000064
关键词
Vitamin E analogues; Mitochondrial targeting; Reactive oxygen species; Respiratory complexes; Apoptosis; Mesothelioma
资金
- Australian Research Council of Australia
- National Health and Medical Research Council of Australia, and Cancer Council Queensland
- Czech Science Foundation [P301/10/1937, P305/12/1708]
- Apoptosis Research Group of the School of Medical Science, Griffith University
Malignant mesothelioma (MM) is a fatal neoplastic disease with no therapeutic option. Therefore, the search for novel therapies is of paramount importance. Methods: Since mitochondrial targeting of alpha-tocopheryl succinate (alpha-TOS) by its tagging with triphenylphosphonium enhances its cytotoxic effects to cancer cells, we tested its effect on MM cells and experimental mesotheliomas. Results: Mitochondrially targeted vitamin E succinate (MitoVES) was more efficient in killing MM cells than a-TOS with IC50 lower by up to two orders of magnitude. Mitochondrial association of MitoVES in MM cells was documented using its fluorescently tagged analogue. MitoVES caused apoptosis in MM cells by mitochondrial destabilization, resulting in the loss of mitochondrial membrane potential, generation of reactive oxygen species, and destabilization of respiratory supercomplexes. The role of the mitochondrial complex II in the activity of MitoVES was confirmed by the finding that MM cells with suppressed succinate quinone reductase were resistant to MitoVES. MitoVES suppressed mesothelioma growth in nude mice with high efficacy. Discussion: MitoVES is more efficient in killing MM cells and suppressing experimental mesotheliomas compared with the non-targeted alpha-TOS, giving it a potential clinical benefit.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据