کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2583505 1130692 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Gambogenic acid induced mitochondrial-dependent apoptosis and referred to Phospho-Erk1/2 and Phospho-p38 MAPK in human hepatoma HepG2 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Gambogenic acid induced mitochondrial-dependent apoptosis and referred to Phospho-Erk1/2 and Phospho-p38 MAPK in human hepatoma HepG2 cells
چکیده انگلیسی

Gambogenic acid, identified from Gamboge, is responsible for anti-tumor effects, and has been shown to be a potential molecule against human cancers. In this study, the molecular mechanism of gambogenic acid-induced apoptosis in HepG2 cells was investigated. Gambogenic acid significantly inhibited cell proliferation and induced apoptosis. Acridine orange/ethidium bromide (AO/EB) staining was used to observe apoptosis, and then confirmed by transmission electron microscopy. Gambogenic acid induced apoptosis and morphological changes in mitochondria, and intracellular reactive oxygen species (ROS) and mitochondrial membrane permeabilization (MMP) in mitochondrial apoptosis pathway were also examined. Results showed that the levels of Phospho-p38 and its downstream Phospho-Erk1/2 of HepG2 cells increased in time- and concentration-dependent manners after gambogenic acid treatments. Additionally, gambogenic acid increased expression ratio of Bcl-2/Bax in mRNA levels, Western blotting analysis also further confirmed the reduced level of Bcl-2 and increase the expression level of Bax in HepG2 cells. These results indicated that gambogenic acid induced mitochondrial oxidative stress and activated caspases through a caspase-3 and caspase-9-dependent apoptosis pathway. Moreover, gambogenic acid mediated apoptosis and was involved in the Phospho-Erk1/2 and Phospho-p38 MAPK proteins expression changes in HepG2 cells.


► Our results illustrated the effects of gambogenic acid on HepG2 cells and found that gambogenic acid inhibit cell proliferation by inducing apoptosis in our study.
► Our studies address the molecular mechanism of apoptosis is initially caused by oxidative stress associated with mitochondrial and then referred to Erk1/2-MAPK and p38-MAPK.
► In addition, Bcl-2 family members and caspase cascade have also contributed to it in the process of apoptosis.
► Our findings provide preliminary experimental evidence supporting relevance for gambogenic acid possibility of considering novel pharmacological treatment strategies in HepG2 cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Environmental Toxicology and Pharmacology - Volume 33, Issue 2, March 2012, Pages 181–190
نویسندگان
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