کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5829278 1558990 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
NG, a novel PABA/NO-based oleanolic acid derivative, induces Human hepatoma cell apoptosis via a ROS/MAPK-dependent mitochondrial pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
NG, a novel PABA/NO-based oleanolic acid derivative, induces Human hepatoma cell apoptosis via a ROS/MAPK-dependent mitochondrial pathway
چکیده انگلیسی
O2-(2,4-dinitro-5-{[2-(12-en-28-β-D- galactopyranosyl-oleanolate-3-yl) -oxy-2-oxoethyl]amino}phenyl)1-(N-hydroxyethylmethylamino)diazen-1-ium-1,2- diolate (NG), a novel PABA/NO-based derivative of oleanolic acid (OA), has been found to show potent antitumor activity both in vivo and in vitro. In the present study, NG could significantly reduce tumor volume and weight in the H22 solid tumor mouse model. Meanwhile, NG showed selective effects on the HepG2 cells including NO generation, cytotoxic effect and apoptosis, which were prevented by hemoglobin (NO scavenger). Moreover, NG-induced apoptosis of HepG2 cells was characteristic of intracellular reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential (Δψm) and enhanced Bax-to-Bcl-2 ratio. The release of apoptotic inducing factor (AIF) and cytochrome c (Cyt c) from mitochondria and the activation of caspase-3, 9 were also detected, indicating that NG may induce apoptosis through a mitochondrial-mediated pathway. Simultaneously, NG treatment could lead to the activation of the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK but not ERK1/2. Treatment with SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38) prior to NG was found to reverse NG-induced apoptosis. Moreover, it was found that antioxidant N-acetylcysteine (NAC) blocked the induction of apoptosis and partly reversed the activation of JNK and p38, up-regulation of Bax, down-regulation of Bcl-2 and the activation of caspase-3 in NG-treated cells. Taking together, these findings suggest that NO can be released from NG, which induces apoptosis through a ROS/MAPK-mediated mitochondrial pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 691, Issues 1–3, 15 September 2012, Pages 61-68
نویسندگان
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