The Efficient Activity of Glabridin and its Derivatives Against EGFRmediated Inhibition of Breast Cancer

  • Authors: Ghosh A.1, Ghosh D.2, Mukerjee N.3, Maitra S.4, Das P.5, Dey A.6, Sharkawi S.7, Zouganelis G.8, Alexiou A.9, Chaudhari S.10, Sharma R.11, Waghmare S.12, Papadakis M.13, Batiha G.14
  • Affiliations:
    1. Microbiology Division, Department of Botany,, Gauhati Universit
    2. Department of Molecular Biology and Biotechnology, Cotton University
    3. Department of Microbiology, West Bengal State University
    4. Department of Microbiology, Adamas University
    5. Central Silk Board, Regional Office
    6. Department of Life Sciences, , Presidency University
    7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University
    8. School of Human Sciences, College of Life and Natural Sciences, University of Derby
    9. Department of Science and Engineering, Novel Global Novel Global Community Educational Foundation
    10. Department of Pharmaceutical Chemistry,, P.E.S Modern College of Pharmacy
    11. Department of Pharmaceutical Chemistry,, University Institute of Pharma Sciences Chandigarh University
    12. , Dr. Vithalrao Vikhe Patil College of Pharmacy,
    13. Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke
    14. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University
  • Issue: Vol 31, No 5 (2024)
  • Pages: 573-594
  • Section: Anti-Infectives and Infectious Diseases
  • URL: https://permmedjournal.ru/0929-8673/article/view/645164
  • DOI: https://doi.org/10.2174/0929867330666230303120942
  • ID: 645164

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Full Text

Abstract

Background:Breast cancer (BC) is one of the most typical causes of cancer death in women worldwide. Activated epidermal growth factor receptor (EGFR) signaling has been increasingly associated with BC development and resistance to cytotoxic drugs. Due to its significant association with tumour metastasis and poor prognosis, EGFR-mediated signaling has emerged as an attractive therapeutic target in BC. Mainly in all BC cases, mutant cells over-expresses EGFR. Certain synthetic drugs are already used to inhibit the EGFR-mediated pathway to cease metastasis, with several phytocompounds also revealing great chemopreventive activities.

Methods:This study used chemo-informatics to predict an effective drug from some selected phytocompounds. The synthetic drugs and the organic compounds were individually screened for their binding affinities, with EGFR being the target protein using molecular docking techniques.

Results:The binding energies were compared to those of synthetic drugs. Among phytocompounds, Glabridin (phytocompound of Glycyrrhiza glabra) manifested the best dock value of -7.63 Kcal/mol, comparable to that of the highly effective anti-cancer drug Afatinib. The glabridin derivatives also exhibited comparable dock values.

Conclusion:The AMES properties deciphered the non-toxic features of the predicted compound. Pharmacophore modeling and in silico cytotoxicity predictions also exhibited a superior result assuring their drug likeliness. Therefore, Glabridin can be conceived as a promising therapeutic method to inhibit EGFR-mediated BC.

About the authors

Arabinda Ghosh

Microbiology Division, Department of Botany,, Gauhati Universit

Author for correspondence.
Email: info@benthamscience.net

Debanjana Ghosh

Department of Molecular Biology and Biotechnology, Cotton University

Email: info@benthamscience.net

Nobendu Mukerjee

Department of Microbiology, West Bengal State University

Email: info@benthamscience.net

Swastika Maitra

Department of Microbiology, Adamas University

Email: info@benthamscience.net

Padmashree Das

Central Silk Board, Regional Office

Email: info@benthamscience.net

Abhijit Dey

Department of Life Sciences, , Presidency University

Email: info@benthamscience.net

Souty Sharkawi

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University

Email: info@benthamscience.net

Georgios Zouganelis

School of Human Sciences, College of Life and Natural Sciences, University of Derby

Email: info@benthamscience.net

Athanasios Alexiou

Department of Science and Engineering, Novel Global Novel Global Community Educational Foundation

Email: info@benthamscience.net

Somdatta Chaudhari

Department of Pharmaceutical Chemistry,, P.E.S Modern College of Pharmacy

Email: info@benthamscience.net

Ritika Sharma

Department of Pharmaceutical Chemistry,, University Institute of Pharma Sciences Chandigarh University

Email: info@benthamscience.net

Sonali Waghmare

, Dr. Vithalrao Vikhe Patil College of Pharmacy,

Email: info@benthamscience.net

Marios Papadakis

Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke

Author for correspondence.
Email: info@benthamscience.net

Gaber Batiha

Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University

Email: info@benthamscience.net

References

  1. Key, T.J.; Verkasalo, P.K.; Banks, E. Epidemiology of breast cancer. Lancet Oncol., 2001, 2(3), 133-140. doi: 10.1016/S1470-2045(00)00254-0 PMID: 11902563
  2. Schroeder, J.A.; Lee, D.C. Transgenic mice reveal roles for TGFalpha and EGF receptor in mammary gland development and neoplasia. J. Mammary Gland Biol. Neoplasia, 1997, 2(2), 119-129. doi: 10.1023/A:1026347629876 PMID: 10882298
  3. Hampton, K.K.; Craven, R.J. Pathways driving the endocytosis of mutant and wild-type EGFR in cancer. Oncoscience, 2014, 1(8), 504-512. doi: 10.18632/oncoscience.67 PMID: 25594057
  4. Lo, H.W.; Hsu, S.C.; Hung, M.C. EGFR signaling pathway in breast cancers: from traditional signal transduction to direct nuclear translocalization. Breast Cancer Res. Treat., 2006, 95(3), 211-218. doi: 10.1007/s10549-005-9011-0 PMID: 16261406
  5. Bhargava, R.; Gerald, W.L.; Li, A.R.; Pan, Q.; Lal, P.; Ladanyi, M.; Chen, B. EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod. Pathol., 2005, 18(8), 1027-1033. doi: 10.1038/modpathol.3800438 PMID: 15920544
  6. Dandawate, P.R.; Subramaniam, D.; Jensen, R.A.; Anant, S. Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy. Semin. Cancer Biol., 2016, 40-41(41), 192-208. doi: 10.1016/j.semcancer.2016.09.001 PMID: 27609747
  7. Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661. doi: 10.1021/acs.jnatprod.5b01055 PMID: 26852623
  8. Siddiqui, J.; Singh, A.; Chagtoo, M.; Singh, N.; Godbole, M.; Chakravarti, B. Phytochemicals for breast cancer therapy: current status and future implications. Curr. Cancer Drug Targets, 2015, 15(2), 116-135. doi: 10.2174/1568009615666141229152256 PMID: 25544650
  9. Aggarwal, B.B.; Sethi, G.; Baladandayuthapani, V.; Krishnan, S.; Shishodia, S. Targeting cell signaling pathways for drug discovery: an old lock needs a new key. J. Cell Biochem., 2007, 102(3), 580-592. doi: 10.1002/jcb.21500 PMID: 17668425
  10. Li, X.; Yang, C.; Wan, H.; Zhang, G.; Feng, J.; Zhang, L.; Chen, X.; Zhong, D.; Lou, L.; Tao, W.; Zhang, L. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur. J. Pharm. Sci., 2017, 110(110), 51-61. doi: 10.1016/j.ejps.2017.01.021 PMID: 28115222
  11. Burris, H.A., III Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib. Oncologist, 2004, 9(S3)(Suppl. 3), 10-15. doi: 10.1634/theoncologist.9-suppl_3-10 PMID: 15163842
  12. Bose, P.; Ozer, H. Neratinib: an oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer. Expert Opin. Investig. Drugs, 2009, 18(11), 1735-1751. doi: 10.1517/13543780903305428 PMID: 19780706
  13. Liu, B.; Diaz Arguello, O.A.; Chen, D.; Chen, S.; Saber, A.; Haisma, H.J. CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation. PLoS One, 2020, 15(5), e0232985. doi: 10.1371/journal.pone.0232985 PMID: 32413049
  14. Kulke, M.H.; Blaszkowsky, L.S.; Ryan, D.P.; Clark, J.W.; Meyerhardt, J.A.; Zhu, A.X.; Enzinger, P.C.; Kwak, E.L.; Muzikansky, A.; Lawrence, C.; Fuchs, C.S. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J. Clin. Oncol., 2007, 25(30), 4787-4792. doi: 10.1200/JCO.2007.11.8521 PMID: 17947726
  15. Janjigian, Y.Y.; Smit, E.F.; Groen, H.J.M.; Horn, L.; Gettinger, S.; Camidge, D.R.; Riely, G.J.; Wang, B.; Fu, Y.; Chand, V.K.; Miller, V.A.; Pao, W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov., 2014, 4(9), 1036-1045. doi: 10.1158/2159-8290.CD-14-0326 PMID: 25074459
  16. Hiscox, S.; Morgan, L.; Barrow, D.; Dutkowski, C.; Wakeling, A.; Nicholson, R.I. Tamoxifen resistance in breast cancer cells is accompanied by an enhanced motile and invasive phenotype: Inhibition by gefitinib (‘Iressa’, ZD1839). Clin. Exp. Metastasis, 2004, 21(3), 201-212. doi: 10.1023/B:CLIN.0000037697.76011.1d PMID: 15387370
  17. Waddell, T.; Chau, I.; Cunningham, D.; Gonzalez, D.; Okines, A.F.C.; Wotherspoon, A.; Saffery, C.; Middleton, G.; Wadsley, J.; Ferry, D.; Mansoor, W.; Crosby, T.; Coxon, F.; Smith, D.; Waters, J.; Iveson, T.; Falk, S.; Slater, S.; Peckitt, C.; Barbachano, Y.; Barbachano, Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol., 2013, 14(6), 481-489. doi: 10.1016/S1470-2045(13)70096-2 PMID: 23594787
  18. Taurin, S.; Allen, K.M.; Scandlyn, M.J.; Rosengren, R.J. Raloxifene reduces triple-negative breast cancer tumor growth and decreases EGFR expression. Int. J. Oncol., 2013, 43(3), 785-792. doi: 10.3892/ijo.2013.2012 PMID: 23842642
  19. Dittmann, K.H.; Mayer, C.; Ohneseit, P.A.; Raju, U.; Andratschke, N.H.; Milas, L.; Rodemann, H.P. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: a COX-2 independent mechanism. Int. J. Radiat. Oncol. Biol. Phys., 2008, 70(1), 203-212. doi: 10.1016/j.ijrobp.2007.08.065 PMID: 17996386
  20. Balakrishnan, S.; Mukherjee, S.; Das, S.; Bhat, F.A.; Raja Singh, P.; Patra, C.R.; Arunakaran, J. Gold nanoparticles- conjugated quercetin induces apoptosis via inhibition of EGFR/PI3K/Akt-mediated pathway in breast cancer cell lines (MCF-7 and MDA-MB-231). Cell Biochem. Funct., 2017, 35(4), 217-231. doi: 10.1002/cbf.3266 PMID: 28498520
  21. Starok, M.; Preira, P.; Vayssade, M.; Haupt, K.; Salomé, L.; Rossi, C. EGFR inhibition by curcumin in cancer cells: a dual mode of action. Biomacromolecules, 2015, 16(5), 1634-1642. doi: 10.1021/acs.biomac.5b00229 PMID: 25893361
  22. Zhu, L.; Shen, X.B.; Yuan, P.C.; Shao, T.L.; Wang, G.D.; Liu, X.P. Arctigenin inhibits proliferation of ER-positive breast cancer cells through cell cycle arrest mediated by GSK3-dependent cyclin D1 degradation. Life Sci., 2020, 256, 117983. doi: 10.1016/j.lfs.2020.117983 PMID: 32565252
  23. Lee, J.; Kim, J.H. Kim. Kaempferol inhibits pancreatic cancer cell growth and migration through the blockade of EGFR-related pathway in vitro. PLoS One, 2016, 11(5), e0155264. doi: 10.1371/journal.pone.0155264 PMID: 27175782
  24. Jaman, M.S.; Sayeed, M.A. Ellagic acid, sulforaphane, and ursolic acid in the prevention and therapy of breast cancer: current evidence and future perspectives. Breast Cancer, 2018, 25(5), 517-528. doi: 10.1007/s12282-018-0866-4 PMID: 29725861
  25. Baraya, Y.S.; Wong, K.K.; Yaacob, N.S.; Nik, S.Y. The immunomodulatory potential of selected bioactive plant-based compounds in breast cancer: a review. Anticancer. Agents Med. Chem., 2017, 17(6), 770-783. PMID: 27539316
  26. Zhang, L.; Chen, H.; Wang, M.; Song, X.; Ding, F.; Zhu, J.; Li, X. Effects of glabridin combined with 5-fluorouracil on the proliferation and apoptosis of gastric cancer cells. Oncol. Lett., 2018, 15(5), 7037-7045. doi: 10.3892/ol.2018.8260 PMID: 29725429
  27. Orry, A.J.W.; Abagyan, R.A.; Cavasotto, C.N. Structure-based development of target-specific compound libraries. Drug Discov. Today, 2006, 11(5-6), 261-266. doi: 10.1016/S1359-6446(05)03717-7 PMID: 16580603
  28. Chandrika, B.B.; Steephan, M.; Kumar, T.R.S.; Sabu, A.; Haridas, M. Hesperetin and Naringenin sensitize HER2 positive cancer cells to death by serving as HER2 Tyrosine Kinase inhibitors. Life Sci., 2016, 160, 47-56. doi: 10.1016/j.lfs.2016.07.007 PMID: 27449398
  29. Jung, S.K.; Kim, J.E.; Lee, S.Y.; Lee, M.H.; Byun, S.; Kim, Y.A.; Lim, T.G.; Reddy, K.; Huang, Z.; Bode, A.M.; Lee, H.J.; Lee, K.W.; Dong, Z. The P110 subunit of PI3-K is a therapeutic target of acacetin in skin cancer. Carcinogenesis, 2014, 35(1), 123-130. doi: 10.1093/carcin/bgt266 PMID: 23913940
  30. Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242. doi: 10.1093/nar/28.1.235 PMID: 10592235
  31. O’Boyle, N.M.; Banck, M.; James, C.A.; Morley, C.; Vandermeersch, T.; Hutchison, G.R. Open Babel: An open chemical toolbox. J. Cheminform., 2011, 3(1), 33. doi: 10.1186/1758-2946-3-33 PMID: 21982300
  32. Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791. doi: 10.1002/jcc.21256 PMID: 19399780
  33. Lipinski, C.A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today. Technol., 2004, 1(4), 337-341. doi: 10.1016/j.ddtec.2004.11.007 PMID: 24981612
  34. Jiang, D.; Li, X.; Wang, H.; Shi, Y.; Xu, C.; Lu, S.; Huang, J.; Xu, Y.; Zeng, H.; Su, J.; Hou, Y.; Tan, L. The prognostic value of EGFR overexpression and amplification in Esophageal squamous cell Carcinoma. BMC Cancer, 2015, 15(1), 377. doi: 10.1186/s12885-015-1393-8 PMID: 25953424
  35. Bowers, K.J.; Chow, D.E.; Xu, H.; Dror, R.O.; Eastwood, M.P.; Gregersen, B.A.; Klepeis, J.L.; Kolossvary, I.; Moraes, M.A.; Sacerdoti, F.D.; Salmon, J.K. Scalable algorithms for molecular dynamics simulations on commodity clusters. SC’06: Proceedings of the 2006 ACM/IEEE Conference on Supercomputing, 2006, , pp. 43-43. doi: 10.1109/SC.2006.54
  36. Chow, E.; Rendleman, C.A.; Bowers, K.J.; Dror, R.O.; Hughes, D.H.; Gullingsrud, J.; Sacerdoti, F.D.; Shaw, D.E. Desmond performance on a cluster of multicore processors. DE Shaw Research Technical Report DESRES/TR--2008-01, 2008.
  37. Shivakumar, D.; Williams, J.; Wu, Y.; Damm, W.; Shelley, J.; Sherman, W. Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force field. J. Chem. Theory Comput., 2010, 6(5), 1509-1519. doi: 10.1021/ct900587b PMID: 26615687
  38. Jorgensen, W.L.; Chandrasekhar, J.; Madura, J.D.; Impey, R.W.; Klein, M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys., 1983, 79(2), 926-935. doi: 10.1063/1.445869
  39. Martyna, G.J.; Tobias, D.J.; Klein, M.L. Constant pressure molecular dynamics algorithms. J. Chem. Phys., 1994, 101(5), 4177-4189. doi: 10.1063/1.467468
  40. Martyna, G.J.; Klein, M.L.; Tuckerman, M. Nosé–Hoover chains: The canonical ensemble via continuous dynamics. J. Chem. Phys., 1992, 97(4), 2635-2643. doi: 10.1063/1.463940
  41. Toukmaji, A.Y.; Board, J.A., Jr Ewald summation techniques in perspective: A survey. Comput. Phys. Commun., 1996, 95(2-3), 73-92. doi: 10.1016/0010-4655(96)00016-1
  42. Kagami, L.P.; das Neves, G.M.; Timmers, L.F.S.M.; Caceres, R.A.; Eifler-Lima, V.L. Geo-Measures: A PyMOL plugin for protein structure ensembles analysis. Comput. Biol. Chem., 2020, 87, 107322. doi: 10.1016/j.compbiolchem.2020.107322 PMID: 32604028
  43. Banerjee, P.; Eckert, A.O.; Schrey, A.K.; Preissner, R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res., 2018, 46(W1), W257-W263. doi: 10.1093/nar/gky318 PMID: 29718510
  44. Leelananda, S.P.; Lindert, S. Computational methods in drug discovery. Beilstein J. Org. Chem., 2016, 12(1), 2694-2718. doi: 10.3762/bjoc.12.267 PMID: 28144341
  45. Aggarwal, B.B.; Kumar, A.; Bharti, A.C. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res., 2003, 23(1A), 363-398. PMID: 12680238
  46. Aggarwal, B.B. Nuclear factor-κB. Cancer Cell, 2004, 6(3), 203-208. doi: 10.1016/j.ccr.2004.09.003 PMID: 15380510
  47. Maadwar, S.; Galla, R. Cytotoxic oxindole derivatives: in vitro EGFR inhibition, pharmacophore modeling, 3D-QSAR and molecular dynamics studies. J. Recept. Signal Transduct. Res., 2019, 39(5-6), 460-469. doi: 10.1080/10799893.2019.1683865 PMID: 31814499

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