Daphnegiravone D from Daphne giraldii Nitsche induces p38-dependent apoptosis via oxidative and nitrosative stress in hepatocellular carcinoma cells - 20/09/18
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Graphical abstract |
Highlights |
• | DGD-induced apoptosis was mediated by oxidative stress. |
• | The generation of nitrosative stress contributes to DGD-induced apoptosis. |
• | DGD triggered an oxidative/nitrosative stress-p38 positive feedback loop. |
Abstract |
Daphnegiravone D (DGD), a prenylated flavonoid from Daphne giraldii Nitsche, significantly inhibited cell growth of several cancer cell lines without cytotoxicity on human normal cells. Our previous study showed that DGD could induce apoptosis in hepatocellular carcinoma Hep3B and HepG2 cells, but the detailed mechanism was still unclear. The present study provides that DGD-induced oxidative and nitrosative stress contribute to apoptotic cell death in Hep3B and HepG2 cells. Furthermore, there is a positive loop between oxidative stress and p38 activation, similar result is observed between nitrosative stress and p38. N-Acetylcysteine (NAC), a reactive oxygen species scavenger, could relieve DGD-induced oxidative stress, but exerts little effect on nitrosative stress. In addition, carboxy-PTIO (PTIO, a well-known scavenger of reactive nitrogen species) down-regulates the induction of nitrosative stress without obvious effect on oxidative stress in DGD-treated cells. In conclusion, the induction of oxidative and nitrosative stress could enhance p38-mediated apoptosis in DGD-treated Hep3B and HepG2 cells. Moreover, we speculated that OS and NS could not ultimately affect each other in DGD-treated HCC cells. This study gives a new insight on the mechanism of DGD-induced apoptotic cell death via oxidative and nitrosative stress in HCC cells.
Le texte complet de cet article est disponible en PDF.Abbreviations : DGD, OS, NS, RNS, SB, NAC, PTIO, H2DCF-DA, DAF-2DA, BCA, Bcl-2, DMEM, PBS, ECL, FBS, HCC, MTT, PARP, PI, PVDF, SDS-PAGE
Keywords : Daphne giraldii Nitsche, Daphnegiravone D, p38, Oxidative stress, Nitrosative stress
Plan
Vol 107
P. 1426-1433 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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