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  • Gamboge is a dry resin obtained from Garcinia hanburyi

    2019-12-02

    Gamboge is a dry resin obtained from Garcinia hanburyi HOOK. f. (Guttiferae). It has a variety of bioactivities, including detoxifying, homeostasis maintaining, anti-inflammatory and parasiticidic effects. Available evidence suggests that gamboge bears anticancer characteristics with gambogenic Cyclic Pifithrin-α hydrobromide (GNA) and gamboge acid (GA) being its main components.. The formula of GNA in GA Bozhou samples is 12.61%, which was published in the Biol. Pharm. Bull [26]. Accumulating evidence demonstrated equal antitumor effect of GNA, showing a wider spectrum of antitumor effect and lower toxicity than that of GA. The simple extraction technology, low cost and obvious anti-tumor effect make it have obvious development and research value. In recent years, our lab has conducted research on the anticancer effects of GNA. Our results show that GNA can inhibit a variety of tumor cells, such as HT-29, K562, A549 [27], CNE-1 [28], HepG-2 [29], U251 [30] and HeLa cells [31], to name a few. Our previous studies showed that GNA inhibits cell growth and proliferation and induces apoptosis in CNE-1 cells [28]. The existing evidence indicates that the VSOR Cl− channels have an effect on NPC. Although some studies have shown that there is variation in the effects of drug activities on VSOR Cl− currents in NPC [32], further exploration is necessary to reveal the mechanism by which VSOR Cl− channel-induced NPC cell apoptosis is induced. In this paper, we hypothesize that VSOR Cl− channels are involved in the GNA-induced apoptosis of CNE-2Z cells. To confirm this hypothesis, we investigated VSOR Cl− currents in CNE-2Z cells treated with GNA. The signaling mechanisms potentially involves in the development of GNA-induced apoptosis in CNE-2Z cells are also discussed.
    Materials and methods
    Results
    Discussion As suggested in a previous study, GNA is capable of inhibiting cell diffusion in non-small cell lung cancer, gastric cancer, liver cancer, colon cancer and ovarian cancer [27,33]. The curative effect of GNA and the mechanisms by which it exerts its effects are a topic of wide concern. GNA exhibited no apparent inhibitory effect on L929 mouse fibroblast cells for 72 h [27], human umbilical vein endothelial cell line was also applied to assess the preferential inhibition and positive result was observed. In this study, the effect of GNA on the activation of chloride channels was measured with the patch clamp technique. The experimental results showed that extracellular perfusion with GNA activated a current with obvious outward dominance. The current direction was consistent with that of chloride ions under different voltages. In addition, DIDS or DCPIB inhibited the current. These effects are in agreement with findings described in the literature [13] and suggest that the current may be a VSOR Cl− current. The concentration of intracellular ions was detected using a chloride-sensitive fluorescent indicator (MQAE) after we quenched the fluorescence intensity of intracellular chloride ions. These results indicate that there is a negative correlation between the fluorescence intensity of MQAE and the concentration of intracellular chloride ions. In addition, the fluorescence intensity of MQAE was higher after treatment with GNA, indicating that the concentration of intracellular chloride ions was lower and that chloride ion channels had opened. Conversely, the fluorescence intensity of the cells declined when DIDS and DCPIB were added, indicating a dramatic increase in the concentration of intracellular chloride ions. These results indicate that GNA promotes the opening of chloride ion channels and increases the efflux of chloride ions, while DIDS and DCPIB have completely opposite effects. Patch clamp experiments demonstrated that GNA activates VSOR Cl− currents in the CNE-2Z cell membrane, and chloride channel blockers suppressed the activation of VSOR Cl− currents in GNA-activated CNE-2Z cells. However, VSOR Cl− channels participate in the regulation of apoptotic volume reduction by mediating the transmembrane transport of chloride ions, and this process may be involved in GNA-induced apoptosis in CNE-2Z cells.