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Article Open Access

Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α

Corrigendum in: /10.3892/mmr.2021.11836
  • Authors:
    • Xiao‑Sa Yang
    • Zhong‑Wei Xu
    • Tai‑Long Yi
    • Rui‑Cheng Xu
    • Jie Li
    • Wen‑Bin Zhang
    • Sai Zhang
    • Hong‑Tao Sun
    • Ze‑Qi Yu
    • Hao‑Xiang Xu
    • Yue Tu
    • Shi‑Xiang Cheng
  • View Affiliations / Copyright

    Affiliations: Institute of TBI and Neuroscience of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of PAP, Tianjin 300162, P.R. China, Central Laboratory of Logistics University of PAP, Tianjin 300309, P.R. China, Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Logistics University of PAP, Tianjin 300309, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5595-5600
    |
    Published online on: February 12, 2018
       https://doi.org/10.3892/mmr.2018.8587
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Abstract

Glioma is one of the most malignant forms of brain tumor, and has been of persistent concern due to its high recurrence and mortality rates, and limited therapeutic options. As a cardiac glycoside, ouabain has widespread applications in congestive heart diseases due to its positive cardiac inotropic effect by inhibiting Na+/K+‑ATPase. Previous studies have demonstrated that ouabain has antitumor activity in several types of human tumor, including glioma. However, the exact underlying mechanism remains to be elucidated. The purpose of present study was to elucidate the effect of ouabain on human glioma cell apoptosis and investigate the exact mechanism. U‑87MG cells were treated with various concentrations of ouabain for 24 h, following which cell viability and survival rate were assessed using a 3‑(4,5-dimethylthiazol-2‑yl)‑2,5‑diphenyltetrazolium bromide assay. The dynamic changes and cell motility were observed using digital holographic microscopy. Additionally, western blot analysis and high‑content screening assays were used to detect the protein expression levels of phosphorylated (p‑)Akt, mammalian target of rapamycin (mTOR), p‑mTOR and hypoxia‑inducible factor (HIF)‑1α, respectively. Compared with the control group, ouabain suppressed U‑87MG cell survival, and attenuated cell motility in a dose‑dependent manner (P<0.01). The downregulation of p‑Akt, mTOR, p‑mTOR and HIF‑1α were observed following treatment with 2.5 and 25 µmol/l of ouabain. These results suggested that ouabain exerted suppressive effects on tumor cell growth and motility, leading to cell death via regulating the intracellular Akt/mTOR signaling pathway and inhibiting the expression of HIF‑1α in glioma cells. The present study examined the mechanism underlying the antitumor property of ouabain, providing a novel potential therapeutic agent for glioma treatment.
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View References

1 

Jain A, Lai JC and Bhushan A: Biochanin A inhibits endothelial cell functions and proangiogenic pathways: Implications in glioma therapy. Anticancer Drugs. 26:323–330. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Bagrov AY, Shapiro JI and Fedorova OV: Endogenous cardiotonic steroids: Physiology, pharmacology, and novel therapeutic targets. Pharmacol Rev. 61:9–38. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Kulikov A, Eva A, Kirch U, Boldyrev A and Scheiner-Bobis G: Ouabain activates signaling pathways associated with cell death in human neuroblastoma. Biochim Biophys Acta. 1768:1691–1702. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Kim N, Yim HY, He N, Lee CJ, Kim JH, Choi JS, Lee HS, Kim S, Jeong E, Song M, et al: Cardiac glycosides display selective efficacy for STK11 mutant lung cancer. Sci Rep. 6:297212016. View Article : Google Scholar : PubMed/NCBI

5 

Xu Z, Wang F, Fan F, Gu Y, Shan N, Meng X, Cheng S, Liu Y, Wang C, Song Y and Xu R: Quantitative proteomics reveals that the inhibition of Na+/K+-ATPase activity affects S-phase progression leading to a chromosome segregation disorder by attenuating the Aurora A function in hepatocellular carcinoma cells. J Proteome Res. 14:4594–4602. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Yan X, Liang F, Li D and Zheng J: Ouabain elicits human glioblastoma cells apoptosis by generating reactive oxygen species in ERK-p66SHC-dependent pathway. Mol Cell Biochem. 398:95–104. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Zhang L, Zhang Z, Guo H and Wang Y: Na+/K+-ATPase-mediated signal transduction and Na+/K+- ATPase regulation. Fundam Clin Pharmacol. 22:615–621. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Desfrere L, Karlsson M, Hiyoshi H, Malmersjö S, Nanou E, Estrada M, Miyakawa A, Lagercrantz H, El Manira A, Lal M and Uhlén P: Na, K-ATPase signal transduction triggers CREB activation and dendritic growth. Proc Natl Acad Sci USA. 106:pp. 2212–2217. 2009; View Article : Google Scholar : PubMed/NCBI

9 

Prassas I and Diamandis EP: Novel therapeutic applications of cardiac glycosides. Nat Rev Drug Discov. 7:926–935. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Wei L, Su YK, Lin CM, Chao TY, Huang SP, Huynh TT, Jan HJ, Whang-Peng J, Chiou JF, Wu AT and Hsiao M: Preclinical investigation of ibrutinib, a Bruton's kinase tyrosine (Btk) inhibitor, in suppressing glioma tumorigenesis and stem cell phenotypes. Oncotarget. 7:69961–69975. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Xie Z: Molecular mechanisms of Na/K-ATPase-mediated signal transduction. Ann N Y Acad Sci. 986:497–503. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Ahmed Z, Deyama Y, Yoshimura Y and Suzuki K: Cisplatin sensitivity of oral squamous carcinoma cells is regulated by Na+, K+-ATPase activity rather than copper-transporting P-type ATPases, ATP7A and ATP7B. Cancer Chemother Pharmacol. 63:643–650. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Lin Y, Ho DH and Newman RA: Human tumor cell sensitivity to oleandrin is dependent on relative expression of Na+, K+-ATPase subunitst. J Exp Ther Oncol. 8:271–286. 2010.PubMed/NCBI

14 

Wu J, Akkuratov EE, Bai Y, Gaskill CM, Askari A and Liu L: Cell signaling associated with Na+/K+-ATPase: Activation of phosphatidylinositide 3-kinase IA/Akt by ouabain is independent of Src. Biochemistry. 52:9059–9067. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Joy A, Kapoor M, Georges J, Butler L, Chang Y, Li C, Crouch A, Smirnov I, Nakada M, Hepler J, et al: The role of AKT isoforms in glioblastoma: AKT3 delays tumor progression. J Neurooncol. 130:43–52. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Clark PA, Bhattacharya S, Elmayan A, Darjatmoko SR, Thuro BA, Yan MB, van Ginkel PR, Polans AS and Kuo JS: Resveratrol targeting of AKT and p53 in glioblastoma and glioblastoma stem-like cells to suppress growth and infiltration. J Neurosurg. 126:1448–1460. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Liu Y, Zheng J, Zhang Y, Wang Z, Yang Y, Bai M and Dai Y: Fucoxanthin activates apoptosis via inhibition of PI3K/Akt/mTOR pathway and suppresses invasion and migration by restriction of p38-MMP-2/9 pathway in human glioblastoma cells. Neurochem Res. 41:2728–2751. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Rapisarda A, Uranchimeg B, Sordet O, Pommier Y, Shoemaker RH and Melillo G: Topoisomerase I-mediated inhibition of hypoxia-inducible factor 1: Mechanism and therapeutic implications. Cancer Res. 64:1475–1482. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Thomas GV, Tran C, Mellinghoff IK, Welsbie DS, Chan E, Fueger B, Czernin J and Sawyers CL: Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med. 12:122–127. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Jensen RL, Ragel BT, Whang K and Gillespie D: Inhibition of hypoxia inducible factor-1alpha (HIF-1alpha) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas. J Neurooncol. 78:233–247. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD, Engh J, Iwama T, Kunisada T, Kassam AB, et al: Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene. 28:3949–3959. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Lum JJ, Bui T, Gruber M, Gordan JD, DeBerardinis RJ, Covello KL, Simon MC and Thompson CB: The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis. Genes Dev. 21:1037–1049. 2007. View Article : Google Scholar : PubMed/NCBI

23 

García-Maceira P and Mateo J: Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: Implications for anticancer therapy. Oncogene. 28:313–324. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang XS, Xu ZW, Yi TL, Xu RC, Li J, Zhang WB, Zhang S, Sun HT, Yu ZQ, Xu HX, Xu HX, et al: Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836. Mol Med Rep 17: 5595-5600, 2018.
APA
Yang, X., Xu, Z., Yi, T., Xu, R., Li, J., Zhang, W. ... Cheng, S. (2018). Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836. Molecular Medicine Reports, 17, 5595-5600. https://doi.org/10.3892/mmr.2018.8587
MLA
Yang, X., Xu, Z., Yi, T., Xu, R., Li, J., Zhang, W., Zhang, S., Sun, H., Yu, Z., Xu, H., Tu, Y., Cheng, S."Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836". Molecular Medicine Reports 17.4 (2018): 5595-5600.
Chicago
Yang, X., Xu, Z., Yi, T., Xu, R., Li, J., Zhang, W., Zhang, S., Sun, H., Yu, Z., Xu, H., Tu, Y., Cheng, S."Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836". Molecular Medicine Reports 17, no. 4 (2018): 5595-5600. https://doi.org/10.3892/mmr.2018.8587
Copy and paste a formatted citation
x
Spandidos Publications style
Yang XS, Xu ZW, Yi TL, Xu RC, Li J, Zhang WB, Zhang S, Sun HT, Yu ZQ, Xu HX, Xu HX, et al: Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836. Mol Med Rep 17: 5595-5600, 2018.
APA
Yang, X., Xu, Z., Yi, T., Xu, R., Li, J., Zhang, W. ... Cheng, S. (2018). Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836. Molecular Medicine Reports, 17, 5595-5600. https://doi.org/10.3892/mmr.2018.8587
MLA
Yang, X., Xu, Z., Yi, T., Xu, R., Li, J., Zhang, W., Zhang, S., Sun, H., Yu, Z., Xu, H., Tu, Y., Cheng, S."Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836". Molecular Medicine Reports 17.4 (2018): 5595-5600.
Chicago
Yang, X., Xu, Z., Yi, T., Xu, R., Li, J., Zhang, W., Zhang, S., Sun, H., Yu, Z., Xu, H., Tu, Y., Cheng, S."Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α Corrigendum in /10.3892/mmr.2021.11836". Molecular Medicine Reports 17, no. 4 (2018): 5595-5600. https://doi.org/10.3892/mmr.2018.8587
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