Vitamin E analogs, a novel group of "Mitocans," as anticancer agents: The importance of being redox-silent

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Neuzil, Jiri
Tomasetti, Marco
Zhao, Yan
Dong, Lan-Feng
Birringer, Marc
Wang, Xiu-Fang
Low, Pauline
Wu, Kun
Salvatore, Brian A
Ralph, Steven J
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Joan Heller Brown

Date
2007
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Abstract

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 redoxsilence is a prerequisite property for most of the anticancer activities described in this communication.

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Molecular Pharmacology

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71

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5

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© 2007 ASPET. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the author for more information.

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Biochemistry and cell biology

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Pharmacology and pharmaceutical sciences

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