Gambogenic acid mediated apoptosis through the mitochondrial oxidative stress and inactivation of Akt signaling pathway in human nasopharyngeal carcinoma CNE-1 cells.

Abstract

In the present study, Gambogenic acid exhibits potential anti-tumor activity in several cancer cell lines. However, Gambogenic acid-induced apoptosis mechanism is not well understood. Here, we report that Gambogenic acid was capable to induce CNE-1 cells apoptosis and caused mitochondrial and endoplasmic reticulum injury, analyzed via transmission electron microscopy and acridine orange/ethidium bromide (AO/EB) double staining. To quantitatively analyze apoptosis, through the propidium iodide (PI)/Annexin V-FITC double staining to detect cell apoptosis, PI staining of the cell cycle distribution. To further explore the potential mechanism of Gambogenic acid mediated apoptosis in CNE-1 cells, we also examined mitochondrial oxidative stress in the levels of reactive oxygen species, the release of cytochrome c, intracellular Ca(2+) concentration and mitochondrial membrane potential by flow cytometry. Moreover, Gambogenic acid could result in a time and concentration-dependent decrease in Phospho-Akt expression, basal expression levels of Akt change was not obvious, In addition, we detected Bcl-2 family including Bcl-2, Bax and Bad expression in mRNA level. This resulted in a decrease of Bcl-2 and Bad increased in CNE-1 cells after Gambogenic acid treatment. Overall, our results indicated that Gambogenic acid mediated apoptosis through inactivation of Akt, accompanied with mitochondrial oxidative stress and cross-talk with Bcl-2 family in the process of apoptosis.

• Authors: Fenggen Yan, Mei Wang, Hui Chen, Jingjing Su, Xiaoshan Wang, Fei Wang, Lunzhu Xia, Qinglin Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 652 Issue 1-3 Pg. 23-32 (Feb 10 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21118682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier B.V. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Terpenes
• Xanthenes
• Xanthones
• bcl-2-Associated X Protein
• neo-gambogic acid
• Oncogene Protein v-akt

Topics

• Apoptosis (drug effects)
• Carcinoma
• Cell Proliferation (drug effects)
• Humans
• Mitochondria (drug effects, metabolism)
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (metabolism, pathology)
• Oncogene Protein v-akt (metabolism)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Terpenes (pharmacology)
• Tumor Cells, Cultured
• Xanthenes
• Xanthones (pharmacology)
• bcl-2-Associated X Protein (metabolism)