DOI QR코드

DOI QR Code

Plant Phenolics Ferulic Acid and P-Coumaric Acid Inhibit Colorectal Cancer Cell Proliferation through EGFR Down-Regulation

  • Roy, Nabarun (Distributed Information Centre, Kerala Agricultural University) ;
  • Narayanankutty, Arunaksharan (Amala Cancer Research Centre, University of Calicut) ;
  • Nazeem, PA (Distributed Information Centre, Kerala Agricultural University) ;
  • Valsalan, Ravisankar (Distributed Information Centre, Kerala Agricultural University) ;
  • Babu, TD (Amala Cancer Research Centre, University of Calicut) ;
  • Mathew, Deepu (Distributed Information Centre, Kerala Agricultural University)
  • Published : 2016.08.01

Abstract

Background: Colorectal cancer (CRC) or bowel cancer is one of the most important cancer diseases, needing serious attention. The cell surface receptor gene human epidermal growth factor receptor (EGFR) may have an important role in provoking CRC. In this pharmaceutical era, it is always attempted to identify plant-based drugs for cancer, which will have less side effects for human body, unlike the chemically synthesized marketed drugs having serious side effects. So, in this study the authors tried to assess the activity of two important plant compounds, ferulic acid (FA) and p-coumaric acid (pCA), on CRC. Materials and Methods: FA and pCA were tested for their cytotoxic effects on the human CRC cell line HCT 15 and also checked for the level of gene expression of EGFR by real time PCR analysis. Positive results were confirmed by in silico molecular docking studies using Discovery Studio (DS) 4.0. The drug parallel features of the same compounds were also assessed in silico. Results: Cytotoxicity experiments revealed that both the compounds were efficient in killing CRC cells on a controlled concentration basis. In addition, EGFR expression was down-regulated in the presence of the compounds. Docking studies unveiled that both the compounds were able to inhibit EGFR at its active site. Pharmacokinetic analysis of these compounds opened up their drug like behaviour. Conclusions: The findings of this study emphasize the importance of plant compounds for targeting diseases like CRC.

Keywords

Colorectal cancer;EGFR;ferulic acid;p-coumaric acid;molecular docking;cytotoxicity

Acknowledgement

Supported by : Council for Scientific and Industrial Research, Govt. of India

References

  1. Arnold M, Sierra MS, Laversanne M, et al (2016). Global patterns and trends in colorectal cancer incidence and mortality. Gut.
  2. Bergstrom CA (2005). In silico predictions of drug solubility and permeability: two rate-limiting barriers to oral drug absorption. Basic Clin Pharmacol Toxicol, 96, 156-61. https://doi.org/10.1111/j.1742-7843.2005.pto960303.x
  3. Berridge MV, Herst PM, Tan AS (2005). Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev, 11, 127-52.
  4. Branden G, Sjogren T, Schnecke V, et al (2014). Structure-based ligand design to overcome CYP inhibition in drug discovery projects. Drug Discov Today, 19, 905-11. https://doi.org/10.1016/j.drudis.2014.03.012
  5. Deller MC, Rupp B (2015). Models of protein-ligand crystal structures: trust, but verify. J Comput Aided Mol Des, 29, 817-36. https://doi.org/10.1007/s10822-015-9833-8
  6. Doak BC, Zheng J, Dobritzsch D, et al (2016). How beyond rule of 5 drugs and clinical candidates bind to their targets. J Med Chem, 59, 2312-27. https://doi.org/10.1021/acs.jmedchem.5b01286
  7. Du X, Li Y, Xia YL, et al (2016). Insights into protein-ligand interactions: mechanisms, models, and methods. Int J Mol Sci, 17, 144. https://doi.org/10.3390/ijms17020144
  8. El-Seedi HR, El-Said AM, Khalifa SA, et al (2012). Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids. J Agric Food Chem, 60, 10877-95. https://doi.org/10.1021/jf301807g
  9. Favoriti P, Carbone G, Greco M, et al (2016). Worldwide burden of colorectal cancer: a review. Updates Surg, 68, 7-11. https://doi.org/10.1007/s13304-016-0359-y
  10. Ferlay J, Soerjomataram I, Dikshit R, et al (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 136, 359-86. https://doi.org/10.1002/ijc.29210
  11. Hammond WA, Swaika A, Mody K (2016). Pharmacologic resistance in colorectal cancer: a review. Ther Adv Med Oncol, 8, 57-84. https://doi.org/10.1177/1758834015614530
  12. Hatok J, Babusikova E, Matakova T, et al (2009). In vitro assays for the evaluation of drug resistance in tumor cells. Clin Exp Med, 9, 1-7. https://doi.org/10.1007/s10238-008-0011-3
  13. Hou T, Li Y, Zhang W, et al (2009). Recent developments of in silico predictions of intestinal absorption and oral bioavailability. Comb Chem High Throughput Screen, 12, 497-506. https://doi.org/10.2174/138620709788489082
  14. Katya T, Michel B, Aloise M, et al (2009). ADDME-avoiding drug development mistakes early: central nervous system drug discovery perspective. BMC Neurol, 9, 1. https://doi.org/10.1186/1471-2377-9-1
  15. Kim S, Thiessen PA, Bolton EE, et al (2016). PubChem substance and compound databases. Nucleic Acids Res, 44, 1202-13. https://doi.org/10.1093/nar/gkv951
  16. Koosha S, Alshawsh MA, Looi CY, et al (2016). An association map on the effect of flavonoids on the signaling pathways in colorectal cancer. Int J Med Sci, 13, 374-85. https://doi.org/10.7150/ijms.14485
  17. Kubista M, Andrade JM, Bengtsson M, et al (2006). The realtime polymerase chain reaction. Mol Aspects Med, 27, 95-125. https://doi.org/10.1016/j.mam.2005.12.007
  18. Lipinski CA (2004). Lead and drug like compounds: the rule of-five revolution. Drug Discov Today Technol, 1, 337-41.
  19. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real time quantitative PCR and the 2 -${\Delta}{\Delta}$CT method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  20. Mancuso C, Santangelo R (2014). Ferulic acid: pharmacological and toxicological aspects. Food Chem Toxicol, 65, 185-95. https://doi.org/10.1016/j.fct.2013.12.024
  21. Mohan CG, Gandhi T, Garg D, et al (2007). Computer-assisted methods in chemical toxicity prediction. Mini Rev Med Chem, 7, 499-507. https://doi.org/10.2174/138955707780619554
  22. Moroy G, Martiny VY, Vayer P, et al (2012). Toward in silico structure-based ADMET prediction in drug discovery. Drug Discov Today, 17, 44-55. https://doi.org/10.1016/j.drudis.2011.10.023
  23. Narayanankutty A, Mukesh RK, Ayoob SK, et al (2016). Virgin coconut oil maintains redox status and improves glycemic conditions in high fructose fed rats. J Food Sci Tech, 53, 895-901. https://doi.org/10.1007/s13197-015-2040-8
  24. Pabla B, Bissonnette M, Konda VJ (2015). Colon cancer and the epidermal growth factor receptor: current treatment paradigms, the importance of diet, and the role of chemoprevention. World J Clin Oncol, 6, 133-41. https://doi.org/10.5306/wjco.v6.i5.133
  25. Park JM, Lee HJ, Yoo JH, et al (2015). Overview of gastrointestinal cancer prevention in Asia. Best Pract Res Clin Gastroenterol, 29, 855-67. https://doi.org/10.1016/j.bpg.2015.09.008
  26. Pei K, Ou J, Huang J, et al (2016). P-coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities. J Sci Food Agric, 96, 2952-62. https://doi.org/10.1002/jsfa.7578
  27. Pollastri MP (2010). Overview on the Rule of Five. Curr Protoc Pharmacol, 9, 12.
  28. Pospisil P, Ballmer P, Scapozza L, et al (2003). Tautomerism in computer-aided drug design. J Recept Signal Transduct Res, 23, 361-71. https://doi.org/10.1081/RRS-120026975
  29. Rose PW, Prlic A, Bi C, et al (2015). The RCSB Protein Data Bank: views of structural biology for basic and applied research and education. Nucleic Acids Res, 43, 345-56. https://doi.org/10.1093/nar/gku1214
  30. Stierand K, Rarey M (2010). Drawing the PDB: protein-ligand complexes in two dimensions. ACS Med Chem Lett, 1, 540-5. https://doi.org/10.1021/ml100164p
  31. Sumantran VN (2011). Cellular chemosensitivity assays: an overview. Methods Mol Biol, 731, 219-36.
  32. Tian S, Wang J, Li Y, et al (2015). The application of in silico drug-likeness predictions in pharmaceutical research. Adv Drug Deliv Rev, 86, 2-10. https://doi.org/10.1016/j.addr.2015.01.009
  33. Torre LA, Siegel RL, Ward EM, et al (2016). Global cancer incidence and mortality rates and trends-an update. Cancer Epidemiol Biomarkers Prev, 25, 16-27. https://doi.org/10.1158/1055-9965.EPI-15-0578
  34. Vanommeslaeghe K, MacKerell AD Jr (2015). CHARMM additive and polarizable force fields for biophysics and computer-aided drug design. Biochim Biophys Acta, 1850, 861-71. https://doi.org/10.1016/j.bbagen.2014.08.004
  35. Veber DF, Johnson SR, Cheng HY, et al (2002). Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem, 45, 2615-23. https://doi.org/10.1021/jm020017n
  36. Wrafter PF, Connelly TM, Khan J, et al (2016). The 100 most influential manuscripts in colorectal cancer: a bibliometric analysis. Surgeon. 2016. [Epub ahead of print]
  37. Wu G, Robertson DH, Brooks CL 3rd, et al (2003). Detailed analysis of grid-based molecular docking: a case study of CDOCKER-a CHARMm-based MD docking algorithm. J Comput Chem, 24, 1549-62. https://doi.org/10.1002/jcc.10306
  38. Yiu AJ, Yiu CY (2016). Biomarkers in colorectal cancer. Anticancer Res, 36, 1093-102.
  39. Yuriev E, Holien J, Ramsland PA (2015). Improvements, trends, and new ideas in molecular docking: 2012-2013 in review. J Mol Recognit, 28, 581-604. https://doi.org/10.1002/jmr.2471