Research: KOVAROVA and COLLEAGUES,

Listed in Issue 238

Abstract

KOVAROVA and COLLEAGUES, Molecular Therapy Group Institute of Biotechnology, Academy of Sciences of the Czech Republic, tested the effect of α-tocopheryl succinate (α-TOS) tagged with triphenylphosphonium upon malignant mesothelioma (MM) cells.

Background

Malignant mesothelioma (MM) is a fatal neoplastic disease with no therapeutic option. Therefore, the search for novel therapies is of paramount importance.

Methodology

Since mitochondrial targeting of α-tocopheryl succinate (α-TOS) by its tagging with triphenylphosphonium enhances its cytotoxic effects to cancer cells, the authors tested its effect on MM cells and experimental mesotheliomas.

Results

Mitochondrially targeted vitamin E succinate (MitoVES) was more efficient in killing MM cells than α-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 super complexes. 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.

Conclusion

MitoVES is more efficient in killing Malignant mesothelioma (MM) cells and suppressing experimental mesotheliomas compared with the non-targeted α-TOS, giving it a potential clinical benefit.

References

Kovarova J, Bajzikova M, Vondrusova M, Stursa J, Goodwin J, Nguyen M, Zobalova R, Pesdar EA, Truksa J, Tomasetti M, Dong LF, Neuzil J. Mitochondrial targeting of α-tocopheryl succinate enhances its anti-mesothelioma  efficacy. Redox Rep. 19(1):16-25. doi: 10.1179/1351000213Y.0000000064. Nov 12 Epub 2013.  Jan 2014.

Comment

This intricately designed research tested the ability of mitochondrial targeted vitamin E succinate (MitoVES) to kill malignant mesothelioma (MM) cells. The results were that MitoVES caused apoptosis in MM cells by mitochondrial destabilization and that mesothelioma growth was suppressed. Research to more deeply discover the role of metabolically, i.e. mitochondrially driven processes in cancer is to be applauded and hopefully studied in other systems with other cancers.

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