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Article

Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells

  • Authors:
    • Xiaodong Wang
    • Yuwen Diao
    • Yu Liu
    • Ningning Gao
    • Dong Gao
    • Yanyan Wan
    • Jingjing Zhong
    • Guangyi Jin
  • View Affiliations / Copyright

    Affiliations: Shenzhen Engineering Laboratory of Synthetic Biology, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China
  • Pages: 4750-4758
    |
    Published online on: June 18, 2015
       https://doi.org/10.3892/mmr.2015.3963
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Abstract

Aspirin and isosorbide mononitrate (ISMN) are two commonly used drugs, which are clinically applied for the treatment of inflammatory and cardiovascular diseases, respectively. Recently, aspirin has attracted interest due to its potential application for the treatment of cancer, particularly colon cancer. NO-aspirin, an aspirin derivative containing a covalently bound NO-donating moiety, has been proven to be an effective anti‑tumor agent with apoptosis-inducing ability. In the present study, ISMN was used as an NO donor and its synergic effect with aspirin was assessed in human colon cancer cells. In vitro, an MTT assay demonstrated that ISMN had a synergistic effect on the growth inhibitory effects of aspirin on HCT116 and SW620 colon cancer cells, while the growth of EA.hy926 normal endothelial cells was unaffected. This synergistic anti‑tumor effect was further validated in vivo using nude mouse HCT116 cell xenograft model. Observation of nuclear morphology, Annexin V-fluorescein isothiocyanate/propidium iodide double staining and a caspase-3 activity assay suggested that the combination of the two drugs induced apoptosis in HCT116 cells. Furthermore, the molecular mechanisms of the apoptotic effect of the drugs was assessed using an NO release assay, reverse transcription quantitative polymerase chain reaction analysis, western blot analysis and a luciferase reporter assay. It was certified that the increase in the amount of NO release, the decrease in the luciferase promoter activity and the expression of cyclin D1 and c-myc in HCT116 cells were affected by aspirin and ISMN in a synergistic manner. In conclusion, the present study was the first, to the best of our knowledge, to report on the synergistic apoptosis-inducing effects of aspirin and ISMN in human colon cancer cells, which were mediated via Wnt and NO signaling pathways. The results of the present study will facilitate the development of future therapeutic strategies.
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1 

Hossain MA, Kim DH, Jang JY, Kang YJ, Yoon JH, Moon JO, Chung HY, Kim GY, Choi YH, Copple BL, et al: Aspirin induces apoptosis in vitro and inhibits tumor growth of human hepatocellular carcinoma cells in a nude mouse xenograft model. Int J Oncol. 40:1298–1304. 2012.

2 

Fuster V and Sweeny JM: Aspirin: A historical and contemporary therapeutic overview. Circulation. 123:768–778. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Dovizio M, Bruno A, Tacconelli S and Patrignani P: Mode of action of aspirin as a chemopreventive agent. Recent Results Cancer Res. 191:39–65. 2013. View Article : Google Scholar

4 

Jankowska H, Hooper P and Jankowski JA: Aspirin chemoprevention of gastrointestinal cancer in the next decade. A review of the evidence. Pol Arch Med Wewn. 120:407–412. 2010.PubMed/NCBI

5 

Goel A, Chang DK, Ricciardiello L, Gasche C and Boland CR: A novel mechanism for aspirin-mediated growth inhibition of human colon cancer cells. Clin Cancer Res. 9:383–390. 2003.PubMed/NCBI

6 

Cooper K, Squires H, Carroll C, Papaioannou D, Booth A, Logan RF, Maguire C, Hind D and Tappenden P: Chemoprevention of colorectal cancer: Systematic review and economic evaluation. Health Technol Assess. 14:1–206. 2010. View Article : Google Scholar

7 

Chen C, Hu JT, Tu YJ, Wu JC, Liang J, Gao LL, Wang ZG, Yang BF and Dong DL: Effects of isosorbide mononitrate on the restoration of injured artery in mice in vivo. Eur J Pharmacol. 640:150–156. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Kaufman R, Nunes I, Bolognese JA, Miller DL, Salotti D, McCarthy JM, Smith WB, Herman GA and Feig PU: Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens. 4:311–318. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Wallace JL and Del Soldato P: The therapeutic potential of NO-NSAIDs. Fundam Clin Pharmacol. 17:11–20. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Pipili-Synetos E, Papageorgiou A, Sakkoula E, Sotiropoulou G, Fotsis T, Karakiulakis G and Maragoudakis ME: Inhibition of angiogenesis, tumour growth and metastasis by the NO-releasing vasodilators, isosorbide mononitrate and dinitrate. Br J Pharmacol. 116:1829–1834. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Usman MW, Luo F, Cheng H, Zhao JJ and Liu P: Chemopreventive effects of aspirin at a glance. Biochim Biophys Acta. 1855:254–263. 2015.PubMed/NCBI

12 

Tan Z, Shang X, Li L, Tian L, Ma Y, Peng Y and Gao L: Clinical study of isosorbide mononitrate treatment for angina pectoris in coronary heart disease. Exp Ther Med. 5:1133–1136. 2013.PubMed/NCBI

13 

Palmer RM, Ferrige AG and Moncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 327:524–526. 1987. View Article : Google Scholar : PubMed/NCBI

14 

Ignarro L: Nitric oxide biology and pathobiology. 2nd edition. Academic Press; New York: 2009

15 

Shah V, Lyford G, Gores G and Farrugia G: Nitric oxide in gastrointestinal health and disease. Gastroenterology. 126:903–913. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Xu W, Liu LZ, Loizidou M, Ahmed M and Charles IG: The role of nitric oxide in cancer. Cell Res. 12:311–320. 2002. View Article : Google Scholar

17 

Mocellin S, Bronte V and Nitti D: Nitric oxide, a double edged sword in cancer biology: Searching for therapeutic opportunities. Med Res Rev. 27:317–352. 2007. View Article : Google Scholar

18 

Rigas B and Kashfi K: Nitric-oxide-donating NSAIDs as agents for cancer prevention. Trends Mol Med. 10:324–330. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Williams JL, Nath N, Chen J, Hundley TR, Gao J, Kopelovich L, Kashfi K and Rigas B: Growth inhibition of human colon cancer cells by nitric oxide (NO)-donating aspirin is associated with cyclooxygenase-2 induction and beta-catenin/T-cell factor signaling, nuclear factor-kappaB, and NO synthase 2 inhibition: Implications for chemoprevention. Cancer Res. 63:7613–7618. 2003.PubMed/NCBI

20 

Khan NI, Cisterne A, Baraz R, Bradstock KF and Bendall LJ: Para-NO-aspirin inhibits NF-kappaB and induces apoptosis in B-cell progenitor acute lymphoblastic leukemia. Exp Hematol. 40:207–215. e12012. View Article : Google Scholar

21 

Yang Y, Yang JJ, Tao H and Jin WS: New perspectives on beta-catenin control of cell fate and proliferation in colon cancer. Food Chem Toxicol. 74:14–19. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Yang Y: Wnt signaling in development and disease. Cell Biosci. 2:142012. View Article : Google Scholar : PubMed/NCBI

23 

Lu D, Cottam HB, Corr M and Carson DA: Repression of beta-catenin function in malignant cells by nonsteroidal antiin-flammatory drugs. Proc Natl Acad Sci USA. 102:18567–18571. 2005. View Article : Google Scholar

24 

Nath N, Liu X, Jacobs L and Kashfi K: Flurbiprofen benzyl nitrate (NBS-242) inhibits the growth of A-431 human epidermoid carcinoma cells and targets β-catenin. Drug Des Devel Ther. 7:389–396. 2013.

25 

Kang YJ, Park HJ, Chung HJ, Min HY, Park EJ, Lee MA, Shin Y and Lee SK: Wnt/β-catenin signaling mediates the antitumor activity of magnolol in colorectal cancer cells. Mol Pharmacol. 82:168–177. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Diao Y, Liu Y, Gao N, Gao D, Wan Y, Zhong J and Jin G: Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells. Mol Med Rep 12: 4750-4758, 2015.
APA
Wang, X., Diao, Y., Liu, Y., Gao, N., Gao, D., Wan, Y. ... Jin, G. (2015). Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells. Molecular Medicine Reports, 12, 4750-4758. https://doi.org/10.3892/mmr.2015.3963
MLA
Wang, X., Diao, Y., Liu, Y., Gao, N., Gao, D., Wan, Y., Zhong, J., Jin, G."Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells". Molecular Medicine Reports 12.3 (2015): 4750-4758.
Chicago
Wang, X., Diao, Y., Liu, Y., Gao, N., Gao, D., Wan, Y., Zhong, J., Jin, G."Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells". Molecular Medicine Reports 12, no. 3 (2015): 4750-4758. https://doi.org/10.3892/mmr.2015.3963
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Diao Y, Liu Y, Gao N, Gao D, Wan Y, Zhong J and Jin G: Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells. Mol Med Rep 12: 4750-4758, 2015.
APA
Wang, X., Diao, Y., Liu, Y., Gao, N., Gao, D., Wan, Y. ... Jin, G. (2015). Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells. Molecular Medicine Reports, 12, 4750-4758. https://doi.org/10.3892/mmr.2015.3963
MLA
Wang, X., Diao, Y., Liu, Y., Gao, N., Gao, D., Wan, Y., Zhong, J., Jin, G."Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells". Molecular Medicine Reports 12.3 (2015): 4750-4758.
Chicago
Wang, X., Diao, Y., Liu, Y., Gao, N., Gao, D., Wan, Y., Zhong, J., Jin, G."Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells". Molecular Medicine Reports 12, no. 3 (2015): 4750-4758. https://doi.org/10.3892/mmr.2015.3963
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