Involvement of enniatins-induced cytotoxicity in human HepG2 cells.
Enniatins (ENNs) are mycotoxins found in Fusarium fungi and they appear in nature as mixtures of cyclic depsipeptides. The ability to form ionophores in the cell membrane is related to their cytotoxicity. Changes in ion distribution between inner and outer phases of the mitochondria affect to their metabolism, proton gradient, and chemiosmotic coupling, so a mitochondrial toxicity analysis of enniatins is highly recommended because they host the homeostasis required for cellular survival. Two ENNs, ENN A and ENN B on hepatocarcinoma cells (HepG2) at 1.5 and 3 μM and three exposure times (24, 48 and 72 h) were studied. Flow cytometry was used to examine their effects on cell proliferation, to characterize at which phase of the cell cycle progression the cells were blocked and to study the role of the mitochondrial in ENNs-induced apoptosis. In conclusion, apoptosis induction on HepG2 cells allowed to compare cytotoxic effects caused by both ENNs, A and B. It is reported the possible mechanism observed in MMP changes, cell cycle analysis and apoptosis/necrosis, identifying ENN B more toxic than ENN A.
Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, València, Spain. ana.juan@uv.es
Ana
A
Juan-García
Lara
L
Manyes
María-José
MJ
Ruiz
Guillermina
G
Font
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000633:toxicity*; D005670:Fusarium / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects; D009183:Mycotoxins / Q000633:toxicity*; D011419:Propidium / Q000378:metabolism
D047630:Depsipeptides; D009183:Mycotoxins; C100264:enniatins; D011419:Propidium