Avicins, natural anticancer saponins, permeabilize mitochondrial membranes.
Avicins are a class of natural saponins with selective pro-apoptotic activity in cancer cells. In this work, we studied the influence of avicins on metabolic state of rat liver mitochondria. Avicin-treated mitochondria underwent a significant decrease in oxygen consumption rate that was completely restored by addition of exogenous cytochrome c. On the other hand, avicins increased the rotenone-insensitive oxidation of external NADH in the presence of exogenous cytochrome c, long before high amplitude swelling of mitochondria was observed. The increase in external NADH oxidation was cyclosporin A-insensitive. Avicin G significantly accelerated hydroperoxide-induced oxidation of mitochondrial endogenous NAD(P)H, the drop of the inner membrane potential and the high amplitude swelling of mitochondria. The obtained data might explain selective induction of apoptosis in tumor cells by avicins. Based on other studies showing that tumor cells generate hydroperoxides with a very high rate, avicins could provide a new strategy of anticancer therapy by sensitizing cells with high levels of reactive oxygen species to apoptosis.
Lemeshko
Victor V
VV
Escuela de Física, Facultad de Ciencias, Universidad Nacional de Colombia, sede Medellín, AA3840 Medellín, Colombia. vvasilie@unal.edu.co
Haridas
Valsala
V
Quijano Pérez
Jairo C
JC
Gutterman
Jordan U
JU
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000187:drug effects*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D012503:Saponins; C478446:avicin G; D012402:Rotenone; D009243:NAD; D009249:NADP; C478445:avicin D; D016572:Cyclosporine; D045304:Cytochromes c; D006861:Hydrogen Peroxide