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

Su, Jingjing; Xu, Ting; Jiang, Genling; Hou, Mei; Liang, Man; Cheng, Hui; Li, Qinglin

doi:10.1016/j.fitote.2019.01.002

Cited by 23 publications

(16 citation statements)

References 33 publications

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“…If ER stress worsens, heavy chain-binding protein (Bip) serves as the primary sensor in the activation of the UPR. We found that Bip mRNA (Figure 3A) was upregulated by GNA, consistent with previous studies (Su et al, 2019). As shown in Figure 3B, GNA increased the mRNA expression of Chop, a downstream target of the UPR, which can induce apoptosis (Hu et al, 2018).…”

Section: Gambogenic Acid Induced Apoptosis By Activating Endoplasmic Reticulum Stresssupporting

confidence: 90%

“…The molecular mechanisms of GNA mainly include regulating NF-κB signalling (Zhou et al, 2020), activating volume-sensitive outwardly rectifying chloride channels (Su et al, 2019) and increasing the level of apoptosis-related proteins (Huang et al, 2019). We found that GNA interacts with the Aurora A by shift assay, suggesting that the Aurora A signalling pathway may be a new target of GNA against CRC cells.…”

Section: Discussionmentioning

confidence: 80%

“…Previous studies have reported that GNA induces apoptosis via mitochondrial dependence (Yan et al, 2012) and death receptors (Zhou et al, 2013). Although it has been reported that GNA triggers ER stress-mediated apoptosis through the reactive oxygen species/IRE1α/c-Jun N-terminal kinase signalling pathway in CRC (Zhao et al, 2020) and triggers apoptosis via heavy chain-binding protein (Bip), ATF4 and C/EBP-homologous protein (Chop) in nasopharyngeal carcinoma (Su et al, 2019), the mechanism of GNA-induced ER stress is still incomplete. In the present study, we will deeply investigate the effects of GNA-induced ER stress on CRC in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Gambogenic Acid Induces Endoplasmic Reticulum Stress in Colorectal Cancer via the Aurora A Pathway

Liu

Guo

et al. 2021

Front. Cell Dev. Biol.

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Colorectal cancer (CRC) is one of the most common malignancies in the world and has a poor prognosis. In the present research, gambogenic acid (GNA), isolated from the traditional Chinese medicine gamboge, markedly induced apoptosis and inhibited the proliferation of CRC in vitro and in vivo. Furthermore, GNA triggered endoplasmic reticulum (ER) stress, which subsequently activated inositol-requiring enzyme (IRE) 1α and the eukaryotic translation initiation factor (eIF) 2α pathway. Pretreatment with salubrinal (an eIF2α inhibitor) rescued GNA-induced cell death. Furthermore, GNA downregulated the expression of Aurora A. The Aurora A inhibitor alisertib decreased ER stress. In human colorectal adenocarcinoma tissue, Aurora A was upregulated compared to normal colorectal epithelial nuclei. Furthermore, GNA ameliorated mouse colitis-associated cancer models. Our findings demonstrated that GNA significantly inhibited the proliferation of CRC through activation of ER stress by regulating Aurora A, which indicates the potential of GNA for preventing the progression of CRC.

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Section: Gambogenic Acid Induced Apoptosis By Activating Endoplasmic Reticulum Stresssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Gambogenic Acid Induces Endoplasmic Reticulum Stress in Colorectal Cancer via the Aurora A Pathway

Liu

Guo

et al. 2021

Front. Cell Dev. Biol.

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“…13) In previous studies, we found that GNA can resist cancer by regulating multiple programmed cell death patterns such as autophagy and apoptosis, and there was already a variety of evidence that GNA could reverse tumor resistance. [14][15][16] However, the molecular mechanism of GNA regulates autophagy and apoptosis in Adriamycin (ADM) resistant hcc cells has not been elucidated. Therefore, in this study, we investigated the role of GNA in reversing ADM resistance in hcc cells through in vitro experiments and further explored the interaction between autophagy and apoptosis during the reversal.…”

Section: Introductionmentioning

confidence: 99%

Gambogenic Acid Inhibits Basal Autophagy of Drug-Resistant Hepatoma Cells and Improves Its Sensitivity to Adriamycin

Wang

Zhan²,

Cheng

et al. 2022

Biological & Pharmaceutical Bulletin

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Gambogenic acid (GNA) is extracted from plant Gamboge, has a wide range of anti-tumor effects. In this paper, we study the inhibitory effect of GNA on the BEL-7402/ADM of hepatoma resistant cell lines and further study the mechanism of action. Cell viability test represented that GNA could improve the sensitivity of hepatoma drug-resistant cell line BEL-7402/ADM to Adriamycin (ADM), and further study by 4′,6-diamidino-2-phenylindole (DAPI) staining and flow cytometry found that GNA could improve the effect of ADM on promoting apoptosis in BEL-7402/ADM cells, and the activation of apoptosis-related protein was significantly increased, and the ratio of Bax to Bcl-2 was significantly increased. Monodansylcadaverine staining and transmission electron microscopy showed that the basal autophagy level of BEL-7402/ADM cells was higher than that of BEL-7402 cells. Further detection of protein expression found that the intracellular LC3-II to LC3-I ratio and Beclin 1 protein expression increased in the combination of GNA and ADM, but the protein level of p62 increased significantly. GNA inhibit protective autophagy in BEL-7402/ADM cells and promote the role of ADM in inducing apoptosis, thereby increasing ADM sensitivity to BEL-7402/ADM cells, and the effect of GNA inhibition of autophagy may be achieved by inhibiting the degradation of autophagosomes.

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“…Meanwhile, it also has a promising anti-tumor effect in vitro and in vivo, which can inhibit the growth of a variety of tumor cells and induce tumor cell apoptosis (Li et al, 2010;Yu et al, 2012). For example, it has been reported that GNA inhibits the proliferation of small cell lung cancer cells by impeding cell cycle and inducing apoptosis (Huang et al, 2019); additionally, GNA induces apoptosis and inhibits cell proliferation by activating endoplasmic reticulum stress in nasopharyngeal carcinoma cells (Su et al, 2019). However, the anti-tumor mechanism of GNA needs further study.…”

Section: Introductionmentioning

confidence: 99%

Gambogenic acid suppresses bladder cancer cells growth and metastasis by regulating NF‐κB signaling

2020

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Background Gambogenic acid (GNA) is one of the main active components of Gamboge, and its anticancer role has been reported in some cancers. The study was to investigate the inhibitory effects of GNA on the proliferation and metastasis of bladder cancer (BC) cells and its potential regulatory mechanisms. Materials and Methods BC cell lines (BIU‐87 cells, T24 cells, and J82 cells) were treated with different doses of GNA for different time, and then the effects of GNA on BC cell were examined in vitro using CCK‐8 assay, apoptosis assays, and Transwell tests. NF‐κB signaling activity was detected by the NF‐κB p65 luciferase reporter assay. Western blot was used to detect the expressions of cIAP2, XIAP, Survivin, and p65. Results GNA inhibited the viability of BC cells in vitro in a dose‐ and time‐dependent manner and facilitated apoptosis of BC cells. Moreover, GNA could remarkably impede the migration and invasion abilities of BC cells. In terms of mechanism, GNA administration reduced the activity of NF‐κB signaling and down‐regulated the expressions of p65, survivin, XIAP, and cIAP2. Conclusion GNA blocks the growth and metastasis of BC cells via inhibiting the NF‐κB signal transduction pathway.

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

Cited by 23 publications

References 33 publications

Gambogenic Acid Induces Endoplasmic Reticulum Stress in Colorectal Cancer via the Aurora A Pathway

Gambogenic Acid Induces Endoplasmic Reticulum Stress in Colorectal Cancer via the Aurora A Pathway

Gambogenic Acid Inhibits Basal Autophagy of Drug-Resistant Hepatoma Cells and Improves Its Sensitivity to Adriamycin

Gambogenic acid suppresses bladder cancer cells growth and metastasis by regulating NF‐κB signaling

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