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The synergistic effect of mefenamic acid with ionizing radiation in colon cancer

  • Seyed Jalal HosseinimehrEmail author
  • Zahar Safavi
  • Sahar Kangarani Farahani
  • Zohreh Noaparst
  • Arash Ghasemi
  • Hossein Asgarian-Omran
Article
  • 23 Downloads

Abstract

Despite radiotherapy is an effective regimen in cancer treatment, resistance to tumor therapy still is a major challenge to radiotherapy and results in cancer recurrence and metastasis. Then the sensitization of tumor cells to ionizing radiation (IR) would be beneficial in cancer treatment. The aim of this study was to evaluate the synergistic effect of mefenamic acid (MEF) on colon cancer cell (HT-29) exposure to IR. HT-29 cells were treated with MEF and then exposed to IR. The synergistic effect of MEF is evaluated by clonogenic assay and flow cytometry. The productions of reactive oxygen species (ROS) were determined in irradiated and treated cells with MEF. The findings of this study showed that MEF had anti-cancer effect on colon cancer cell line and it increased the apoptosis in irradiated HT-29 cells. Also MEF reduced the number of cell colonies when HT-29 cells pre-treated with MEF and irradiated. MEF increased ROS production in irradiated cells. This additive effect of MEF with IR in killing of HT-29 cell was observed at low (10 μM) and medium (100 μM) concentrations of MEF. The present study demonstrates that MEF to be an additive effect on apoptosis and cell death induced by IR in colon cancer cells.

Keywords

Mefenamic acid Synergistic, radiosensitizing Apoptosis Ionizing radiation 

Notes

Acknowledgements

This study was supported by a grant from Mazandaran University of Medical Sciences, Sari, Iran.

Author contributions

SJH conceived and designed research. ZS, SKF, ZN, AG and HAO conducted experiments. SJH and HAO analyzed data. SJH wrote the manuscript. All authors read and approved the manuscript.

Compliance with ethical standards

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

All authors declare that they have no conflict of interest.

References

  1. Anwar S, Welbourn H, Hill J, Sebag-Montefiore D (2013) Adenocarcinoma of the anal canal - a systematic review. Color Dis 15(12):1481–1488.  https://doi.org/10.1111/codi.12325 CrossRefGoogle Scholar
  2. Araujo MR, Campos LC, Damasceno KA, Gamba CO, Ferreira E, Cassali GD (2016) HER-2, EGFR, Cox-2 and Ki67 expression in lymph node metastasis of canine mammary carcinomas: association with clinical-pathological parameters and overall survival. Res Vet Sci 106:121–130.  https://doi.org/10.1016/j.rvsc.2016.03.020 CrossRefGoogle Scholar
  3. Armagan G, Turunc E, Kanit L, Yalcin A (2012) Neuroprotection by mefenamic acid against D-serine: involvement of oxidative stress, inflammation and apoptosis. Free Radic Res 46(6):726–739.  https://doi.org/10.3109/10715762.2012.669836 CrossRefGoogle Scholar
  4. Asanuma M, Nishibayashi-Asanuma S, Miyazaki I, Kohno M, Ogawa N (2001) Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals. J Neurochem 76(6):1895–1904CrossRefGoogle Scholar
  5. August EM, Nguyen T, Malinowski NM, Cysyk RL (1994) Non-steroidal anti-inflammatory drugs and tumor progression: inhibition of fibroblast hyaluronic acid production by indomethacin and mefenamic acid. Cancer Lett 82(1):49–54CrossRefGoogle Scholar
  6. Chen Z, Liu M, Liu X, Huang S, Li L, Song B et al (2013) COX-2 regulates E-cadherin expression through the NF-kappaB/snail signaling pathway in gastric cancer. Int J Mol Med 32(1):93–100.  https://doi.org/10.3892/ijmm.2013.1376 CrossRefGoogle Scholar
  7. Cho HJ, Ahn KC, Choi JY, Hwang SG, Kim WJ, Um HD et al (2015) Luteolin acts as a radiosensitizer in nonsmall cell lung cancer cells by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade. Int J Oncol 46(3):1149–1158.  https://doi.org/10.3892/ijo.2015.2831 CrossRefGoogle Scholar
  8. Choi JY, Cho HJ, Hwang SG, Kim WJ, Kim JI, Um HD et al (2015) Podophyllotoxin acetate enhances gamma-ionizing radiation-induced apoptotic cell death by stimulating the ROS/p38/caspase pathway. Biomed Pharmacother 70:111–118.  https://doi.org/10.1016/j.biopha.2014.12.038 CrossRefGoogle Scholar
  9. Cryer B, Feldman M (1998) Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med 104(5):413–421CrossRefGoogle Scholar
  10. Hamaguchi T, Shinkuma D, Yamanaka Y, Mizuno N (1986) Bioavailability of mefenamic acid: influence of food and water intake. J Pharm Sci 75(9):891–893CrossRefGoogle Scholar
  11. Hosseinimehr SJ (2007) Trends in the development of radioprotective agents. Drug Discov Today 12(19–20):794–805.  https://doi.org/10.1016/j.drudis.2007.07.017 CrossRefGoogle Scholar
  12. Hosseinimehr SJ (2010) Flavonoids and genomic instability induced by ionizing radiation. Drug Discov Today 15(21):907–918CrossRefGoogle Scholar
  13. Hosseinimehr SJ, Nobakht R, Ghasemi A, Pourfallah TA (2015) Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes. Radiat Oncol J 33(3):256–260.  https://doi.org/10.3857/roj.2015.33.3.256 CrossRefGoogle Scholar
  14. Karran P (2000) DNA double strand break repair in mammalian cells. Curr Opin Genet Dev 10(2):144–150CrossRefGoogle Scholar
  15. Lee SL, Son AR, Ahn J, Song JY (2014) Niclosamide enhances ROS-mediated cell death through c-Jun activation. Biomed Pharmacother 68(5):619–624.  https://doi.org/10.1016/j.biopha.2014.03.018 CrossRefGoogle Scholar
  16. Li S, Ma X, Ma L, Wang C, He Y, Yu Z (2013) Effects of ectopic HER-2/neu gene expression on the COX-2/PGE2/P450arom signaling pathway in endometrial carcinoma cells: HER-2/neu gene expression in endometrial carcinoma cells. J Exp Clin Cancer Res 32:11.  https://doi.org/10.1186/1756-9966-32-11 CrossRefGoogle Scholar
  17. Lin F, Luo J, Gao W, Wu J, Shao Z, Wang Z et al (2013) COX-2 promotes breast cancer cell radioresistance via p38/MAPK-mediated cellular anti-apoptosis and invasiveness. Tumour Biol 34(5):2817–2826.  https://doi.org/10.1007/s13277-013-0840-x CrossRefGoogle Scholar
  18. Mahadik M, Dhaneshwar S, Bhavsar R (2012) A high performance liquid chromatography-tandem mass spectrometric method for the determination of mefenamic acid in human plasma: application to pharmacokinetic study. Biomed Chromatogr 26(10):1137–1142.  https://doi.org/10.1002/bmc.1755 CrossRefGoogle Scholar
  19. Mahajan K, Mahajan NP (2015) Cross talk of tyrosine kinases with the DNA damage signaling pathways. Nucleic Acids Res 43(22):10588–10601.  https://doi.org/10.1093/nar/gkv1166 CrossRefGoogle Scholar
  20. Malik A, Sultana M, Qazi A, Qazi MH, Parveen G, Waquar S et al (2016) Role of natural Radiosensitizers and Cancer cell Radioresistance: an update. Anal Cell Pathol (Amst) 2016:6146595–6146598.  https://doi.org/10.1155/2016/6146595 Google Scholar
  21. Meng Z, Gan YH (2015) Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization. Biochem Biophys Res Commun 460(2):198–204.  https://doi.org/10.1016/j.bbrc.2015.03.008 CrossRefGoogle Scholar
  22. Misra S, Sharma K (2014) COX-2 signaling and cancer: new players in old arena. Curr Drug Targets 15(3):347–359CrossRefGoogle Scholar
  23. Montero AJ, Jassem J (2011) Cellular redox pathways as a therapeutic target in the treatment of cancer. Drugs 71(11):1385–1396.  https://doi.org/10.2165/11592590-000000000-00000 CrossRefGoogle Scholar
  24. Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ (2009) Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid. Biochemistry 48(31):7353–7355.  https://doi.org/10.1021/bi900999z CrossRefGoogle Scholar
  25. Regulski M, Regulska K, Prukala W, Piotrowska H, Stanisz B, Murias M (2016) COX-2 inhibitors: a novel strategy in the management of breast cancer. Drug Discov Today 21(4):598–615.  https://doi.org/10.1016/j.drudis.2015.12.003 CrossRefGoogle Scholar
  26. Salehifar E, Hosseinimehr SJ (2016) The use of cyclooxygenase-2 inhibitors for improvement of efficacy of radiotherapy in cancers. Drug Discov Today 21(4):654–662.  https://doi.org/10.1016/j.drudis.2016.02.019 CrossRefGoogle Scholar
  27. Shiiba M, Yamagami H, Yamamoto A, Minakawa Y, Okamoto A, Kasamatsu A et al (2017) Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity. Oncol Rep 37(4):2025–2032.  https://doi.org/10.3892/or.2017.5480 CrossRefGoogle Scholar
  28. Soriano-Hernandez AD, Madrigal-Perez D, Galvan-Salazar HR, Martinez-Fierro ML, Valdez-Velazquez LL, Espinoza-Gomez F et al (2015) Anti-inflammatory drugs and uterine cervical cancer cells: antineoplastic effect of meclofenamic acid. Oncol Lett 10(4):2574–2578.  https://doi.org/10.3892/ol.2015.3580 CrossRefGoogle Scholar
  29. Woo DH, Han IS, Jung G (2004) Mefenamic acid-induced apoptosis in human liver cancer cell-lines through caspase-3 pathway. Life Sci 75(20):2439–2449.  https://doi.org/10.1016/j.lfs.2004.04.042 CrossRefGoogle Scholar
  30. Wu QB, Sun GP (2015) Expression of COX-2 and HER-2 in colorectal cancer and their correlation. World J Gastroenterol 21(20):6206–6214.  https://doi.org/10.3748/wjg.v21.i20.6206 CrossRefGoogle Scholar
  31. Yazdannejat H, Hosseinimehr SJ, Ghasemi A, Pourfallah TA, Rafiei A (2016) Losartan sensitizes selectively prostate cancer cell to ionizing radiation. Cell Mol Biol (Noisy-le-grand) 62(1):30–33Google Scholar
  32. Zhu M, Zhu Y, Lance P (2013) TNFalpha-activated stromal COX-2 signalling promotes proliferative and invasive potential of colon cancer epithelial cells. Cell Prolif 46(4):374–381.  https://doi.org/10.1111/cpr.12047 CrossRefGoogle Scholar
  33. Zou Z, Chang H, Li H, Wang S (2017) Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis 22(11):1321–1335.  https://doi.org/10.1007/s10495-017-1424-9 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research CenterMazandaran University of Medical SciencesSariIran
  2. 2.Department of Radiology and Radiation Oncology, Faculty of MedicineMazandaran University of Medical SciencesSariIran
  3. 3.Department of Immunology, School of MedicineMazandaran University of Medical SciencesSariIran
  4. 4.Immunogenetics Research Center, School of MedicineMazandaran University of Medical SciencesSariIran

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