Gambogenic acid triggers apoptosis in human nasopharyngeal carcinoma CNE-2Z cells by activating volume-sensitive outwardly rectifying chloride channel.

Abstract

Gambogenic acid (GNA) is one of the main components of Gamboge, and its anti-cancer effects have been well confirmed by previous researches. Nasopharyngeal carcinoma (NPC) has not been thoroughly studied, and the pathogenesis of NPC is unclear. Scientists have neither discovered effective therapies nor achieved a desirable prognosis. Some studies have found that the regulation of intra- and extracellular ion channels hinges directly on cell apoptosis, and treatment with GNA brings changes to the volume-sensitive outwardly rectifying chloride (VSOR Cl-) current of CNE-2Z cells recorded by the patch clamp method. Nevertheless, rarely have any researchers probed into the relevance between this variation and the anti-tumor mechanism of GNA. This paper is suggested that 2.0 μmol/L GNA activates VSOR Cl- currents on CNE-2Z cell membranes and that the activation of VSOR Cl- currents by GNA in CNE-2Z cells is blocked by the chloride channel blockers DIDS (400 μmol/L) and DCPIB (20 μmol/L). MQAE experiment further proves that GNA leads to the opening of chloride ion channel, which in turn results in the efflux of VSOR Cl- current; GNA induces the downregulation of GRP78 and the upregulation of ATF4 and CHOP proteins. These effects are correlated with endoplasmic reticulum (ER) stress. GNA can activate VSOR Cl- channels, leading to ER stress, inducing apoptosis and inhibiting proliferation in CNE-2Z cells.

• Authors: Jingjing Su, Ting Xu, Genling Jiang, Mei Hou, Mengru Liang, Hui Cheng, Qinglin Li
• Journal: Fitoterapia (Fitoterapia) Vol. 133 Pg. 150-158 (Mar 2019) ISSN: 1873-6971 [Electronic] Netherlands
• PMID: 30654125 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• ATF4 protein, human
• Chloride Channels
• Chlorides
• DDIT3 protein, human
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• Xanthenes
• Activating Transcription Factor 4
• Transcription Factor CHOP
• neo-gambogic acid

Topics

• Activating Transcription Factor 4 (metabolism)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Chloride Channels (metabolism)
• Chlorides (analysis)
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress
• Garcinia (chemistry)
• Heat-Shock Proteins (metabolism)
• Humans
• Nasopharyngeal Carcinoma (drug therapy, metabolism)
• Nasopharyngeal Neoplasms (drug therapy, metabolism)
• Transcription Factor CHOP (metabolism)
• Xanthenes (pharmacology)