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Plant Science Today (PST)

Research Articles

Early Access

Molecular docking and ADME evaluation of plant-based bioactive molecules targeting nonsense-mediated mRNA decay pathway factors to modulate tumorigenesis

DOI
https://doi.org/10.14719/pst.3737
Submitted
20 April 2024
Published
31-10-2024
Versions

Abstract

Cancer is a global health challenge that requires continuous efforts to discover effective anticancer drugs. Phytochemicals are compounds found in plants that often have medicinal properties. They possess a wide range of bioactive properties, including anticancer activity. Their multiple mechanisms of action in different physiological processes in humans make them promising candidates in the anticancer therapeutics development. The presence of these compounds makes plants valuable resources for traditional medicine and modern pharmaceutical research as well. Natural products from plants and marine sources are being used to find new anticancer agents. In humans, different cellular pathways are involved in the tumorigenesis process. Many studies have shown the role of the nonsense-mediated mRNA decay (NMD) pathway in the process of tumorigenesis. This NMD pathway is controlled by multiple proteins. In this study, we conducted a molecular docking analysis of 50 phytochemicals against the human NMD factor up-frameshit2 (UPF2) protein. The results of the molecular docking experiment and ADME properties indicate that 4 of these molecules (Genistein, Trihydroxyflavone, Baicalein and Epigallocatechin) have the potential to modulate the NMD pathway. Furthermore, these molecules comply with Lipinski's rule of five. The effects of these 4 phytochemicals may be further evaluated using in vitro and in vivo methods for novel anticancer therapeutic development.

References

  1. Marie-Ange Majérus. The cause of cancer: The unifying theory. Adv Cancer Biol. – Metastasis. 2022;4:100034. https://doi.org/10.1016/j.adcanc.2022.100034
  2. Ocran Mattila P, Ahmad R, Hasan SS, Babar ZU. Availability, affordability, access and pricing of anti-cancer medicines in low-and middle-income countries: a systematic review of literature. Frontiers in Public Health. 2021 Apr 30;9:628744. https://doi.org/10.3389/fpubh.2021.628744
  3. Choudhari AS, Mandave PC, Deshpande M, Ranjekar P, Prakash O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Frontiers in Pharmacology. 2020 Jan 28;10:1614. https://doi.org/10.3389/fphar.2019.01614
  4. Rizeq B, Gupta I, Ilesanmi J, AlSafran M, Rahman MM, Ouhtit A. The power of phytochemicals combination in cancer chemoprevention. Journal of Cancer. 2020;11(15):4521. https://doi.org/10.7150/jca.34374
  5. Mazurakova A, Samec M, Koklesova L, et al. Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine — comprehensive effects of phytochemicals in primary, secondary and tertiary care. EPMA Journal. 2022;13:461-86.. https://doi.org/10.1007/s13167-022-00288-z
  6. Prasathkumar M, Anisha S, Dhrisya C, Becky R, Sadhasivam S. Therapeutic and pharmacological efficacy of selective Indian medicinal plants–a review. Phytomedicine Plus. 2021 May 1;1(2):100029. https://doi.org/10.1016/j.phyplu.2021.100029
  7. Panigrahi GK, Sahoo SK, Sahoo A, et al. Bioactive molecules from plants: a prospective approach to combat SARS-CoV-2. Adv Tradit Med (Adtm). 2023;23:617-30. https://doi.org/10.1007/s13596-021-00599-y
  8. George BP, Chandran R, Abrahamse H. Role of phytochemicals in cancer chemoprevention: insights. Antioxidants. 2021;10:1455. https://doi.org/10.3390/antiox10091455
  9. Majrashi TA, Alshehri SA, Alsayari A, Muhsinah AB, Alrouji M, Alshahrani AM, et al. Insight into the biological roles and mechanisms of phytochemicals in different types of cancer: Targeting cancer therapeutics. Nutrients. 2023;15(7):1704.https://doi.org/10.3390/nu15071704
  10. Chirumbolo S, Bjorklund G, Lysiuk R, Vella A, Lenchyk L, Upyr T. Targeting cancer with phytochemicals via their fine tuning of the cell survival signaling pathways. International Journal of Molecular Sciences. 2018;19(11):3568. https://doi.org/10.3390/ijms19113568
  11. Chaudhary Chaudhary T, Chahar A, Sharma JK, Kaur K, Dang A. Phytomedicine in the treatment of cancer: a health technology assessment. Journal of Clinical and Diagnostic Research: JCDR. 2015 Dec;9(12):XC04.
  12. Jorge MB Vítor, Filipa F Vale. Alternative therapies for Helicobacter pylori: probiotics and phytomedicine. FEMS Immunology and Medical Microbiology. November 2011;63(2):153-64. https://doi.org/10.1111/j.1574-695X.2011.00865.x
  13. Ds R, Panigrahi GK. Messenger RNA surveillance: current understanding, regulatory mechanisms and future implications. Molecular Biotechnology. 2024;1-18. https://doi.org/10.1007/s12033-024-01062-4
  14. Patro I, Sahoo A, Nayak BR, et al. Nonsense-mediated mRNA decay: Mechanistic insights and physiological significance. Molecular Biotechnology. 2023. https://doi.org/10.1007/s12033-023-00927-4
  15. Panigrahi GK, Satapathy KB. Sacrificed surveillance process favours plant defense: a review. Plant Archives. 2020;20(1): 2551-59.
  16. Panigrahi GK, Sahoo A, Satapathy KB. Insights to plant immunity: Defense signaling to epigenetics. Physiological and Molecular Plant Pathology. 2021;113:1-7. https://doi.org/10.1016/j.pmpp.2020.101568
  17. Marija Petric Howe, Rickie Patani. Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration. Trends in Neurosciences. 2023;46(10): https://doi.org/10.1016/j.tins.2023.07.001
  18. Karousis ED, Nasif S, Mühlemann O. Nonsense-mediated mRNA decay: novel mechanistic insights and biological impact. Wiley Interdiscip Rev RNA. 2016 Sep;7(5):661-82. https://doi.org/10.1002/wrna.1357
  19. López-Perrote A, Castaño R, Melero R, Zamarro T, Kurosawa H, Ohnishi T, et al. Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex. Nucleic Acids Research. 2016;44(4):1909-23. https://doi.org/10.1093/nar/gkv1527
  20. Clerici M, Deniaud A, Boehm V, Gehring NH, Schaffitzel C, Cusack S. Structural and functional analysis of the three MIF4G domains of nonsense-mediated decay factor UPF2. Nucleic Acids Research. 2014 Feb 1;42(4):2673-86. https://doi.org/10.1093/nar/gkt1197
  21. Colón EM, Haddock LA 3rd, Lasalde C, Lin Q, Ramírez-Lugo JS, González CI. Characterization of the mIF4G domains in the RNA surveillance protein Upf2p. Curr Issues Mol Biol. 2023;46(1):244-61. https://doi.org/10.3390/cimb46010017
  22. Nallusamy S, Mannu J, Ravikumar C, Angamuthu K, Nathan B, Nachimuthu K, et al. Exploring phytochemicals of traditional medicinal plants exhibiting inhibitory activity against main protease, spike glycoprotein, RNA-dependent RNA polymerase and non-structural proteins of SARS-CoV-2 through virtual screening. Frontiers in Pharmacology. 2021 Jul 8;12:667704. https://doi.org/10.3389/fphar.2021.667704
  23. Shang A, Cao SY, Xu XY, Gan RY, Tang GY, Corke H, et al. Bioactive compounds and biological functions of garlic (Allium sativum L.). Foods. 2019 Jul 5;8(7):246. https://doi.org/10.3390/foods8070246
  24. Xiong J, Li S, Wang W, Hong Y, Tang K, Luo Q. Screening and identification of the antibacterial bioactive compounds from Lonicera japonica Thunb. leaves. Food Chemistry. 2013 May 1;138(1):327-33. https://doi.org/10.1016/j.foodchem.2012.10.127
  25. Arora C, Verma D, Aslam J, Mahish P. Phytochemicals in medicinal plants: Biodiversity, bioactivity and drug discovery. Berlin, Boston: De Gruyter. 2023. https://doi.org/10.1515/9783110791891
  26. Chi C, Giri SS, Jun JW, Kim HJ, Yun S, Kim SG, Park SC. Immunomodulatory effects of a bioactive compound isolated from Dryopteris crassirhizoma on the grass carp Ctenopharyngodon idella. Journal of Immunology Research. 2016;2016(1):3068913. https://doi.org/10.1155/2016/1719720
  27. Wen CC, Shyur LF, Jan JT, Liang PH, Kuo CJ, Arulselvan P, et al. Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora and Taxillus chinensis inhibit SARS-CoV replication. Journal of Traditional and Complementary Medicine. 2011 Oct 1;1(1):41-50. https://doi.org/10.1016/S2225-4110(16)30055
  28. Deng YF, Aluko RE, Jin Q, Zhang Y, Yuan LJ. Inhibitory activities of baicalin against renin and angiotensin-converting enzyme. Pharmaceutical Biology. 2012 Apr 1;50(4):401-06.https://doi.org/10.3109/13880209.2011.608076
  29. Dabeek WM, Marra MV. Dietary quercetin and kaempferol: Bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients. 2019 Sep 25;11(10):2288. https://doi.org/10.3390/nu11102288
  30. Awuchi CG. Plants, phytochemicals and natural practices in complementary and alternative system of medicine for treatment of central nervous system disorders. International Journal of Food Properties. 2023 Sep 22;26(1):1190-213. https://doi.org/10.1080/10942912.2023.2205039
  31. Chen CJ, Michaelis M, Hsu HK, Tsai CC, Yang KD, Wu YC, et al. Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication. Journal of Ethnopharmacology. 2008 Oct 30;120(1):108-11. https://doi.org/10.1016/j.jep.2008.07.048
  32. O'Boyle NM, Banck M, James CA, et al. Open Babel: An open chemical toolbox. J Cheminform. 2011;3(33). https://doi.org/10.1186/1758-2946-3-33
  33. Garrett M Morris, Ruth Huey, William Lindstrom, Michel F Sanner, Richard K Belew, David S Goodsell, Arthur J Olson. Autodock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Computational Chemistry. 2009;16:2785-91. https://doi.org/10.1002/jcc.21256
  34. Trott O, Olson AJ. AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem. 2010;31(2):455-61. https://doi.org/10.1002/jcc.21334
  35. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717. https://doi.org/10.1038/srep42717
  36. Lipinski CA. Lead- and drug-like compounds: The rule-of-five revolution. Drug Discovery Today: Technologies. 2004;1:337-41. https://doi.org/10.1016/j.ddtec.2004.11.007
  37. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. Journal of Medicinal Chemistry. 2002 Jun 6;45(12):2615-23. https://doi.org/10.1021/jm020017n
  38. Jung HW, Panigrahi GK, Jung G-Y, Lee YJ, Shin KH, Sahoo A, et al. PAMP-triggered immunity involves proteolytic degradation of core nonsense-mediated mRNA decay factors during early defense response. The Plant Cell. 2020;32(4):1081-101. https://doi.org/10.1105/tpc.19.00631
  39. Sahoo A, Satapathy KB. Differential expression of Arabidopsis EJC core proteins under short-day and long-day growth conditions. Plant Science Today. 2021;8(4):815-19. https://doi.org/10.14719/pst.2021.8.4.1214
  40. Panigrahi GK, Sahoo A, Satapathy KB. Differential expression of selected Arabidopsis resistant genes under abiotic stress conditions. Plant Science Today. 2021;8(4):859-64. https://doi.org/10.14719/pst.2021.8.4.1213
  41. Panigrahi GK, Satapathy KB. Pseudomonas syringae pv. syringae infection orchestrates the fate of the Arabidopsis J domain containing cochaperone and decapping protein factor 5. Physiological and Molecular Plant Pathology. 2021;113(101598):1-9. https://doi.org/10.1016/j.pmpp.2020.101598
  42. Sahoo A, Satapathy KB, Panigrahi GK. Ectopic expression of disease resistance protein promotes resistance against pathogen infection and drought stress in Arabidopsis. Physiological and Molecular Plant Pathology. 2023;124(101949):1-7. https://doi.org/10.1016/j.pmpp.2023.101949
  43. Panigrahi GK, Sahoo A, Satapathy KB. The processing body component varicose plays a multiplayer role towards stress management in Arabidopsis. Plant Physiology Reports. 2024;1-10. https://doi.org/10.1007/s40502-023-00778-w
  44. Sahoo A, Satapathy KB, Panigrahi GK. Security check: Plant immunity under temperature surveillance. Journal of Plant Biochemistry and Biotechnology. 2024; (33)1-4. https://doi.org/10.1007/s13562-023-00846-0
  45. Behera A, Panigrahi GK, Sahoo A. Nonsense-mediated mRNA decay in human health and diseases: Current understanding, regulatory mechanisms and future perspectives. Molecular Biotechnology. 2024;1-19. https://doi.org/10.1007/s12033-024-01267-7
  46. Panigrahi GK, Satapathy KB. Arabidopsis DCP5, a decapping complexprotein interacts with Ubiquitin-5 in the processing bodies. Plant Archives. 2020;20(1):2243-47.
  47. Panigrahi GK, Satapathy KB. Formation of Arabidopsis poly(A)-specific ribonuclease associated processing bodies in response to pathogenic infection. Plant Archives. 2020;20(2):4907-12.

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