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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
