Protective activity of Theobroma cacao L. phenolic extract on AML12 and MLP29 liver cells by preventing apoptosis and inducing autophagy.
Theobroma cacao L. is known to have potential cardiovascular and cancer chemopreventive activities because of its high content of phenolic phytochemicals and their antioxidant capacities. In this work, we show for the first time that cocoa inhibits drug-triggered liver cytotoxicity by inducing autophagy. Phenolic-rich extracts of both unroasted and roasted cocoa prevented Celecoxib-induced cell viability inhibition in MLP29 liver cells because of the accumulation of G1 cells and cell death. Death prevented by cocoa had hallmarks of apoptosis such as the sub-G1 peak at flow cytometry and activation of Bax expression, together with down-regulation of Bcl-2, released cytochrome c in the cytosol with activation of Caspase 3, indicating that components of the apoptotic pathway such as Bax or upstream are major targets of cocoa phytochemicals. The protective effect of cocoa against liver cytotoxicity by Celecoxib was probably accounted for by inducing the autophagic process, as shown by enhanced Beclin 1 expression and accumulation of monodansylcadaverine in autolysosomes. This fact suggests that apoptosis was prevented by inducing autophagy. Finally, considering all these findings, we suggest that cocoa can be added to the list of natural chemopreventive agents whose potential in hepatopathy prevention and therapy should be evaluated.
Arlorio
Marco
M
DiSCAFF and DFB (Drug and Food Biotechnology) Center, Universita degli Studi del Piemonte Orientale A. Avogadro, Via Bovio, 6, 28100 Novara, Italy. arlorio@pharm.unipmn.it
Bottini
Consuelo
C
Travaglia
Fabiano
F
Locatelli
Monica
M
Bordiga
Matteo
M
Coïsson
Jean Daniel
JD
Martelli
Aldo
A
Tessitore
Luciana
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002099:Cacao / Q000737:chemistry*; D000068579:Celecoxib; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control; D052246:Cyclooxygenase 2 Inhibitors / Q000633:toxicity; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006358:Hot Temperature; D051379:Mice; D010636:Phenols / Q000008:administration & dosage*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000633:toxicity; D013449:Sulfonamides / Q000633:toxicity
D052246:Cyclooxygenase 2 Inhibitors; D010636:Phenols; D010936:Plant Extracts; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib