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Biotechnology Letters

, Volume 40, Issue 2, pp 257–262 | Cite as

Inhibition of epidermal growth factor receptor by ferulic acid and 4-vinylguaiacol in human breast cancer cells

  • S. Sudhagar
  • S. Sathya
  • R. Anuradha
  • G. Gokulapriya
  • Y. Geetharani
  • B. S. Lakshmi
Original Research Paper

Abstract

Objectives

To examine the potential of ferulic acid and 4-vinylguaiacol for inhibiting epidermal growth factor receptor (EGFR) in human breast cancer cells in vitro.

Results

Ferulic acid and 4-vinylguaiacol limit the EGF (epidermal growth factor)-induced breast cancer proliferation and new DNA synthesis. Western blot analysis revealed both ferulic acid and 4-vinylguaiacol exhibit sustained inhibition of EGFR activation through down-regulation of Tyr 1068 autophosphorylation. Molecular docking analysis shows ferulic acid forming hydrogen bond interaction with Lys 745 and Met 793 whereas, 4-vinylguaiacol forms two hydrogen bonds with Phe 856 and exhibits stronger hydrophobic interactions with multiple amino acid residues at the EGFR kinase domain.

Conclusions

Ferulic acid and 4-vinylguaiacol could serve as a potential structure for the development of new small molecule therapeutics against EGFR.

Keywords

Breast cancer Epidermal growth factor receptor Ferulic acid 4-Vinylguaiacol 

Notes

Acknowledgements

The Authors thank University Grants Commission, Government of India for the major research grant (F.No. 40-182/2011 (SR)). We thank departmental level assistance programmes UGC-SAP-DSA-I (No.F.5-6/2015/DSA-I (SAP-II), DST-PURSE, and DBT-BUILDER (BT/PR12153/INF/22/200/2014), Government of India for their support.

Supporting information

Biotransformation of ferulic acid to 4-vinylguaiacol.

Identification of 4-vinylguaiacol.

Supplementary Fig. 113C NMR analysis of ferulic acid and 4-vinylguaiacol.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

10529_2017_2475_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 15 kb)
10529_2017_2475_MOESM2_ESM.pptx (129 kb)
Supplementary material 2 (PPTX 129 kb)

References

  1. Peng YH, Shiao HY, Tu CH, Liu PM, Hsu JT, Amancha PK, Wu JS, Coumar MS, Chen CH, Wang SY, Lin WH, Sun HY, Chao YS, Lyu PC, Hsieh HP, Wu SY (2013) Protein kinase inhibitor design by targeting the Asp-Phe-Gly (DFG) motif: the role of the DFG motif in the design of epidermal growth factor receptor inhibitors. J Med Chem 56:3889–3903CrossRefPubMedGoogle Scholar
  2. Roy N, Narayanankutty A, Nazeem PA, Valsalan R, Babu TD, Mathew D (2016) Plant phenolics ferulic acid and p-coumaric acid inhibit colorectal cancer cell proliferation through EGFR down-regulation. Asian Pac J Cancer Prev 7:4019–4023Google Scholar
  3. Ruan Z, Katiyar S, Kannan N (2017) Computational and experimental characterization of patient derived mutations reveal an unusual mode of regulatory spine assembly and drug sensitivity in EGFR Kinase. Biochemistry 56:22–32CrossRefPubMedGoogle Scholar
  4. Sathya S, Sudhagar S, Sarathkumar B, Lakshmi BS (2014) EGFR inhibition by pentacyclic triterpenes exhibit cell cycle and growth arrest in breast cancer cells. Life Sci 95(1):53–62CrossRefPubMedGoogle Scholar
  5. Serafim TL, Carvalho FS, Marques MP, Calheiros R, Silva T, Garrido J, Milhazes N, Borges F, Roleira F, Silva ET, Holy J, Oliveira PJ (2011) Lipophilic caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells. Chem Res Toxicol 24(5):763–774CrossRefPubMedGoogle Scholar
  6. Shan Y, Arkhipov A, Kim ET, Pan AC, Shaw DE (2013) Transitions to catalytically inactive conformations in EGFR kinase. Proc Natl Acad Sci USA 110:7270–7275CrossRefPubMedPubMedCentralGoogle Scholar
  7. Srinivasan M, Sudheer AR, Menon VP (2007) Ferulic acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr 40:92–100CrossRefPubMedPubMedCentralGoogle Scholar
  8. Wang T, Gong X, Jiang R, Li H, Du W, Kuang G (2016) Ferulic acid inhibits proliferation and promotes apoptosis via blockage of PI3K/Akt pathway in osteosarcoma cell. Am J Transl Res 8:968–980PubMedPubMedCentralGoogle Scholar
  9. Yang GW, Jiang JS, Lu WQ (2015) Ferulic acid exerts anti-angiogenic and anti-tumor activity by targeting fibroblast growth factor receptor 1-mediated angiogenesis. Int J Mol 16:24011–24031CrossRefGoogle Scholar
  10. Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ (2007) Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11:217–227CrossRefPubMedPubMedCentralGoogle Scholar
  11. Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ (2008) The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 105:2070–2075CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  • S. Sudhagar
    • 1
  • S. Sathya
    • 1
  • R. Anuradha
    • 1
  • G. Gokulapriya
    • 1
  • Y. Geetharani
    • 1
  • B. S. Lakshmi
    • 1
  1. 1.Department of BiotechnologyCentre for Food Technology, Anna UniversityChennaiIndia

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