RT Journal Article
SR Electronic
T1 Vitamin E Analogs, a Novel Group of “Mitocans,” as Anticancer Agents: The Importance of Being Redox-Silent
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1185
OP 1199
DO 10.1124/mol.106.030122
VO 71
IS 5
A1 Jiri Neuzil
A1 Marco Tomasetti
A1 Yan Zhao
A1 Lan-Feng Dong
A1 Marc Birringer
A1 Xiu-Fang Wang
A1 Pauline Low
A1 Kun Wu
A1 Brian A. Salvatore
A1 Steven J. Ralph
YR 2007
UL http://molpharm.aspetjournals.org/content/71/5/1185.abstract
AB 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 α-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. The American Society for Pharmacology and Experimental Therapeutics