The ability of mitochondria-targeted anticancer drugs to interact with the energy supply of cancer cells leads to increased accumulation of ROS and activation of the mitochondria-dependent death signaling pathways. Because of their mitochondrial targeting and anticancer roles, these drugs have been termed “mitocans” (1-3). We investigated the pro-apoptotic effects of long chain tocopheryl metabolites namely 13-(6-hydroxy-2,5,7,8,-tetramethylchroman-2-yl)-2,6,10-trimethyl-tridecanoic acid (-tocopherylic acid) and 13-(6-hydroxy-2,8,-dimethylchroman-2-yl)-2,6,10-trimethyl-tridecanoic acid (-tocopherylic acid) and their corresponding alcohols in hepatic adenoma cells (HepG2) by FACS-analysis and observed a strong induction of apoptosis with -tocopherylic acid and -tocopherylic acid, respectively. Western-Blot analysis revealed a mitochondrial derived activation of caspases and PARP-cleavage. We further show that both acids are responsible for the generation of intra-mitochondrial reactive oxygen species (ROS) and for a reduction of the mitochondrial membrane potential (m), which finally lead to the observed apoptotic events. In conclusion, the observed properties of long chain vitamin E metabolites correspond to that of "mitocans" and thus, elevated levels of these metabolites might be able to prevent the uncontrolled proliferation of cancer cells.

Long chain vitamin E metabolites act as "Mitocans"

BUZZONI, Lisa;MANFREDINI, Stefano;
2009

Abstract

The ability of mitochondria-targeted anticancer drugs to interact with the energy supply of cancer cells leads to increased accumulation of ROS and activation of the mitochondria-dependent death signaling pathways. Because of their mitochondrial targeting and anticancer roles, these drugs have been termed “mitocans” (1-3). We investigated the pro-apoptotic effects of long chain tocopheryl metabolites namely 13-(6-hydroxy-2,5,7,8,-tetramethylchroman-2-yl)-2,6,10-trimethyl-tridecanoic acid (-tocopherylic acid) and 13-(6-hydroxy-2,8,-dimethylchroman-2-yl)-2,6,10-trimethyl-tridecanoic acid (-tocopherylic acid) and their corresponding alcohols in hepatic adenoma cells (HepG2) by FACS-analysis and observed a strong induction of apoptosis with -tocopherylic acid and -tocopherylic acid, respectively. Western-Blot analysis revealed a mitochondrial derived activation of caspases and PARP-cleavage. We further show that both acids are responsible for the generation of intra-mitochondrial reactive oxygen species (ROS) and for a reduction of the mitochondrial membrane potential (m), which finally lead to the observed apoptotic events. In conclusion, the observed properties of long chain vitamin E metabolites correspond to that of "mitocans" and thus, elevated levels of these metabolites might be able to prevent the uncontrolled proliferation of cancer cells.
2009
Lington, D.; Buzzoni, Lisa; Manfredini, Stefano; Scharlau, D.; Ristow, M.; Birringer, M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1389736
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