Gambogenic acid mediated apoptosis through the mitochondrial oxidative stress and inactivation of Akt signaling pathway in human nasopharyngeal carcinoma CNE-1 cells.
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.
Anhui Province Key laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
Fenggen
F
Yan
Mei
M
Wang
Hui
H
Chen
Jingjing
J
Su
Xiaoshan
X
Wang
Fei
F
Wang
Lunzhu
L
Xia
Qinglin
Q
Li
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014966:Xanthenes; D044004:Xanthones / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D017382:Reactive Oxygen Species; D013729:Terpenes; D014966:Xanthenes; D044004:Xanthones; D051028:bcl-2-Associated X Protein; C045863:neo-gambogic acid; D051058:Oncogene Protein v-akt