Add time:07/11/2019         Source:sciencedirect.com

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.

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