Gambogenic acid induced mitochondrial-dependent apoptosis and referred to phospho-Erk1/2 and phospho-p38 MAPK in human hepatoma HepG2 cells.

Abstract

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.

• Authors: Fenggen Yan, Mei Wang, Jiaming Li, Hui Cheng, Jingjing Su, Xiaoshan Wang, Haiyun Wu, Lunzhu Xia, Xiaoxiang Li, Hebron C Chang, Qinglin Li
• Journal: Environmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 33 Issue 2 Pg. 181-90 (Mar 2012) ISSN: 1872-7077 [Electronic] Netherlands
• PMID: 22222560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• BAX protein, human
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• Reactive Oxygen Species
• Terpenes
• Xanthenes
• Xanthones
• bcl-2-Associated X Protein
• neo-gambogic acid
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Carcinoma, Hepatocellular (enzymology, genetics, pathology)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cell Proliferation (drug effects)
• Cell Shape (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Hep G2 Cells
• Humans
• Liver Neoplasms (enzymology, genetics, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Microscopy, Electron, Transmission
• Mitochondria (drug effects, enzymology, pathology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA, Messenger (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Terpenes (pharmacology)
• Time Factors
• Xanthenes
• Xanthones (pharmacology)
• bcl-2-Associated X Protein (genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)