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Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway

  • Authors:
    • Yan Zhen Zhang
    • Chun Feng Wang
    • Lian Feng Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2595-2603
    |
    Published online on: April 10, 2018
       https://doi.org/10.3892/or.2018.6361
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Abstract

Cucurbitacin D (CuD), isolated from plants from the Cucurbitaceae family, is a potential antitumour agent since it inhibits proliferation, migration and metastasis of cancer cells. Despite CuD antitumour activity in cancer cells, the effects of CuD on gastric cancer cell lines remain unclear. The present study aimed to investigate the effects of CuD on gastric cancer cell growth and death. Human gastric cancer cell lines (AGS, SNU1 and Hs746T) were cultured and treated with different concentrations of CuD (0, 0.25, 0.5, 1 and 2 µM). Cell proliferation was assessed using Cell Counting Kit‑8 assay. Oxidative stress was evaluated by generation of reactive oxygen species (ROS). Cell apoptosis was assessed by terminal deoxynucleotidyl transferase 2'‑deoxyuridine‑5'‑triphosphate nick‑end labelling (TUNEL) staining. Levels of intracellular Ca2+ and adenosine triphosphate (ATP) were also assessed. In the present study, CuD effectively inhibited cell proliferation, triggered ROS generation and induced apoptosis in gastric cancer cells (AGS, SNU1 and Hs746T). Treatment with CuD increased intracellular Ca2+ and ATP levels. CuD also stimulated the expression of inducible nitric oxide synthase (iNOS), which augmented nitric oxide production. In addition, CuD activated the mitochondrial apoptosis pathway, which increased the expression of Bax and the release of cleaved caspace‑9 (C‑caspase‑9) and cytochrome c, decreased the expression of B‑cell lymphoma 2 (Bcl‑2). The mechanism of action of CuD involved the regulation of the protein kinase B/mechanistic target of rapamycin (Akt/mTOR) pathway. We confirmed the effects of CuD on gastric tumours via an in vivo xenograft gastric tumour model. In conclusion, CuD inhibited Akt and activated the iNOS pathway, leading to higher ROS and nitric oxide production, which accelerated gastric cancer cell apoptosis.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang YZ, Wang CF and Zhang LF: Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway. Oncol Rep 39: 2595-2603, 2018.
APA
Zhang, Y.Z., Wang, C.F., & Zhang, L.F. (2018). Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway. Oncology Reports, 39, 2595-2603. https://doi.org/10.3892/or.2018.6361
MLA
Zhang, Y. Z., Wang, C. F., Zhang, L. F."Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway". Oncology Reports 39.6 (2018): 2595-2603.
Chicago
Zhang, Y. Z., Wang, C. F., Zhang, L. F."Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway". Oncology Reports 39, no. 6 (2018): 2595-2603. https://doi.org/10.3892/or.2018.6361
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang YZ, Wang CF and Zhang LF: Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway. Oncol Rep 39: 2595-2603, 2018.
APA
Zhang, Y.Z., Wang, C.F., & Zhang, L.F. (2018). Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway. Oncology Reports, 39, 2595-2603. https://doi.org/10.3892/or.2018.6361
MLA
Zhang, Y. Z., Wang, C. F., Zhang, L. F."Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway". Oncology Reports 39.6 (2018): 2595-2603.
Chicago
Zhang, Y. Z., Wang, C. F., Zhang, L. F."Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway". Oncology Reports 39, no. 6 (2018): 2595-2603. https://doi.org/10.3892/or.2018.6361
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