QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.106.030122v1 71/5/1185    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Neuzil, J. Articles by Ralph, S. J. Search for Related Content PubMed PubMed Citation Articles by Neuzil, J. Articles by Ralph, S. J.

Minireview

Vitamin E Analogs, a Novel Group of "Mitocans," as Anticancer Agents: The Importance of Being Redox-Silent

Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Queensland, Australia (J.N., L.F.D., X.F.W.); Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic (J.N.); Department of Nutrition and Food, Harbin Medical University, Harbin, Heilongjiang Province, China (Y.Z., K.W.); Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy (M.T.); Institute of Human Nutrition, Friedrich Schiller University, Jena, Germany (M.B.); Genomic Research Centre, School of Medical Science, Griffith University, Southport, Queensland, Australia (P.L., S.J.R.); and Department of Chemistry and Physics, Louisiana State University, Shreveport, Louisiana (B.A.S.)

The search for a selective and efficient anticancer agent for treating all neoplastic disease has yet to deliver a universally suitable compound(s). The majority of established anticancer drugs either are nonselective or lose their efficacy because of the constant mutational changes of malignant cells. Until recently, a largely neglected target for potential anticancer agents was the mitochondrion, showing a considerable promise for future clinical applications. Vitamin E (VE) analogs, epitomized by -tocopheryl succinate, belong to the group of "mitocans" (mitochondrially targeted anticancer drugs). They are selective for malignant cells, cause destabilization of their mitochondria, and suppress cancer in preclinical models. This review focuses on our current understanding of VE analogs in the context of their proapoptotic/anticancer efficacy and suggests that their effect on mitochondria may be amplified by modulation of alternative pathways operating in parallel. We show here that the analogs of VE that cause apoptosis (which translates into their anticancer efficacy) generally do not possess antioxidant (redox) activity and are prototypical of the mitocan group of anticancer compounds. Therefore, by analogy to Oscar Wilde's play The Importance of Being Earnest, we use the motto in the title "the importance of being redox-silent" to emphasize an essentially novel paradigm for cancer therapy, in which redox-silence is a prerequisite property for most of the anticancer activities described in this communication.

Address correspondence to: Dr. Jiri Neuzil, Apoptosis Research Group, Heart Foundation Research Centre, School of Medical Science, Griffith University Gold Coast Campus, Southport, Queensland, Australia. E-mail: j.neuzil{at}griffith.edu.au