INTEGRATING COMPUTITONAL METHOD FOR DRUGGABLE BETA CATENIN INHIBITORY PHYTOCOMPOUND FROM GLYCINE MAX L. SEEDS TO TREAT OVARIAN CANCER
Main Article Content
Keywords
Ovarian Cancer, Wnt/ß-catenin inhibition, Phytocompound, Glycine max L.
Abstract
Ovarian Cancer is the most lethal gynecological malignancy and is ranked asthe seventh leading cause of cancer deaths in females. Wnt signaling is an evolutionarily conserved regulatory pathway that governs numerous normal cellular and developmental processes such as cell fate determination, cell proliferation and migration. However, aberrant Wnt signaling has also been identified as a key mechanism in cancer biology. ß -catenin is the key mediator of the Canonical Wnt pathway. In the absence of a Wnt ligand, ß-catenin is degraded by a destruction complex. The main components of this complex include AXIN, adenomatous polyposis coli (APC), casein kinase 1 (CK1), and glycogen synthase kinase 3ß (GSK3ß), as well as the E3 ligase, ßTrCP. Protein phosphatase 2A (PP2A) is also associated with the ß-catenin destruction complex. AXIN is a scaffolding protein that has interaction sites for multiple proteins including PP2A, APC, GSK3ß, and CK1. The most common genetic alteration in the Wnt/ß-catenin pathway involved in EOC is in the ß-catenin gene, CTNNB1. In EOCs a missense mutation in CTNNB1 was always found within the amino terminal domain. Soybeans (Glycine max L.), a functional food widely consumed in Asia, has been reported as the main source of isoflavones. Phytoestrogen properties of soy isoflavones showed their activity as ligands for estrogen receptors and exhibited the estrogenic potency as reported in the previous in vitro and in vivo studies. The major functional components include Carbohydrates, fats, Proteins, Saponins, Lecithin, Linolenic acid, Linoleic acid, Phytosterols and Isoflavones. Due to these valuable constituents, it possesses multiple therapeutic activities. Current in-silico study showed that Daidzein from G. max L. has maximum binding affinity with beta catenin, which may be ultimately inhibited followed by the inactivation of Wnt/β -Catenin pathway. Moreover, it has been shown to relive sleep disorders, may help managing diabetes, prevents osteoporosis, improves blood circulation and provide good care of pregnancy.
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13. (22 Stamos JL, Weis WI. The beta-catenin destruction complex. Cold Spring Harb Perspect Biol.2013;5(1):a007898)
14. (Stamos JL, Weis WI. The beta-catenin destruction complex. Cold Spring Harb Perspect Biol. 2013;5(1):a007898.).
15. (Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis Vu Hong Loan Nguyen1 , Rebecca Hough1 , Stefanie Bernaudo1 and Chun Peng Nguyen et al.Journal of Ovarian Research (2019) 12:122 https://doi.org/10.1186/s13048-019-0596-z )[27
16. Ref: Wnt/β-Catenin Signaling in Development and Disease, Hans Clevers. DOI 10.1016/j.cell.2006.10.018
17. Pharmacologic Manipulation of Wnt Signaling and Cancer Stem Cells Yann Duchartre1, Yong-Mi Kim1, Michael Kahn2,3 Methods Mol Biol. 2017 ; 1613: 463–478. doi:10.1007/978-1-4939-7027-8_18)).
18. ((Phytochemicals: A Multitargeted Approach to Gynecologic Cancer Therapy Lee Farrand,1 Se-Woong Oh,1 Yong Sang Song,2,3,4 and Benjamin K. TsangHindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 890141, 10 pagehttp://dx.doi.org/10.1155/2014/890141))
19. {{Opportunity, Challenge and Scope of Natural Products in Medicinal Chemistry, 2011: 367-383 ISBN: 978-81-308-0448-4. Soybean constituents and theirfunctional benefits Ajay K. Dixit1, J. I. X. Antony1, Navin K. Sharma1 and Rakesh K. Tiwari2}}
20. Wnt/β-catenin signaling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis Vu Hong Loan Nguyen1 , Rebecca Hough1 , Stefanie Bernaudo1 and Chun Peng Nguyen et al. Journal of Ovarian Research (2019) 12:122 https://doi.org/10.1186/s13048-019-0596-z ) .
21. Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol. 2018;81:17–38
22. Luvero D, Milani A, Ledermann JA. Treatment options in recurrent ovarian cancer: latest evidence and clinical potential. Ther Adv Med Oncol. 2014; 6(5):229–39
23. Coleman RL, Monk BJ, Sood AK, Herzog TJ. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol. 2013;10(4): 211–24].
24. [6 Coleman RL, Monk BJ, Sood AK, Herzog TJ. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol. 2013;10(4): 211–24 ].
25. Rehman HM, Sajjad M, Ali MA, Gul R, Naveed M, Aslam MS, Shinwari K, Bhinder MA, Ghani MU, Saleem M, Rather MA, Ahmad I, Amin A. Identification of RdRp inhibitors against SARS-CoV-2 through E-pharmacophore-based virtual screening, molecular docking and MD simulations approaches. Int J Biol Macromol. 2023 May 15;237:124169. doi: 10.1016/j.ijbiomac.2023.124169. Epub 2023 Mar 28. PMID: 36990409; PMCID: PMC10043960.
26. Gul, R., Hanif, M.U., Gul, F. et al. Molecular Cloning, Expression, Sequence Characterization and Structural Insight of Bubalus bubalis Growth Hormone-Receptor.Mol Biotechnol (2022). https://doi.org/10.1007/s12033-022-00612-y
27. Rehman HM, Sajjad M, Ali MA, Gul R, Irfan M, Naveed M, Bhinder MA, Ghani MU, Hussain N, Said ASA, Al Haddad AHI, Saleem M. Identification of NS2B-NS3 Protease Inhibitors for Therapeutic Application in ZIKV Infection: A Pharmacophore-Based High-Throughput Virtual Screening and MD Simulations Approaches. Vaccines. 2023; 11(1):131. https://doi.org/10.3390/vaccines11010131
28. Shinwari K, Rehman HM, Liu G, Bolkov MA, Tuzankina IA, Chereshnev VA. Novel Disease-Associated Missense Single-Nucleotide Polymorphisms Variants Predication by Algorithms Tools and Molecular Dynamics Simulation of Human TCIRG1 Gene Causing Congenital Neutropenia and Osteopetrosis. Front Mol Biosci. 2022 Apr 28; 9:879875.
29. Asma Ahmed*, Ghazala Irshad, Sania Riaz, Rehana Badar, Sana Javaid Awan, Shafaq, Ambreen Abbas. Polarity based extracts of Glycine max (L.) seeds as therapeutic source for ovarian, uterine and hepato-renal profile of sprague dawley rats with letrozole-induced polycystic ovarian syndrome. (2023). Hunan Daxue Xuebao/Journal of Hunan University Natural Sciences. ISSN：1674-2974 | CN 43-1061 / N. 60 (04): 11- 28. DOI 10.17605/OSF.IO/7YHTW
30. Waris, Ghazala & Ahmed, Asma & Rukhsar, Atoofa & Zahra, Fatima-tu & Malik, Areesha. (2023). FORMONONETIN AS PROMISING THERAPEUTIC INTERVENTION FOR RESTORING OVARIAN, UTERINE, AND HEPATO-RENAL FUNCTIONS IN LETROZOLE-INDUCED,POLYCYSTIC OVARIAN SYNDROME SPRAGUE DAWLEY RATS. Journal of Population Therapeutics and Clinical Pharmacology. 727-735. 10.53555/jptcp.v30i19.3749.
31. Evaluation of the hypoglycemic activity of Morchella conica by targeting protein tyrosine phosphatase 1B. Naeema Begum, Abdul Nasir, Zahida Parveen*, Taj Muhammad, Asma Ahmed, Saira Farman, Nargis Jamila, Mohib Shah, Noor Shad Bibi, Akif Khurshid, Zille Huma, Atif Ali Khan Khalil, Ashraf Albrakati and Gaber El-Saber Batiha. Frontiers in Pharmacology (Ethnopharmacology).2021. 12; 1-12. DOI: 10.3389/fphar.2021.661803.
32. Isolation, Purification and Quantification of Quercetin from Onion (Allium cepa L.). Asma Ahmed, Muhammad Gulfraz, Noman Khalique. Proceedings of Pakistan Academy of Sciences. Vol. 55 (1), March 2018. Page: 79- 86; ISSN 0377-2969.
33. Wu, J., Zhou, T., Wang, Y., Jiang, Y., & Wang, Y. (2021). Mechanisms and Advances in Anti-Ovarian Cancer with Natural Plants Component. Molecules (Basel, Switzerland), 26(19), 5949. https://doi.org/10.3390/molecules26195949
34. Zhang, J., Liu, L., Wang, J., Ren, B., Zhang, L., & Li, W. (2018). Formononetin, an isoflavone from Astragalus membranaceus inhibits proliferation and metastasis of ovarian cancer cells. Journal of ethnopharmacology, 221, 91–99. https://doi.org/10.1016/j.jep.2018.04.014
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Jan 30, 2024
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Samra Hafeez, Asma Ahmed, Maryam Mureed, Hamna shahid, & Afaq Akram. (2024). INTEGRATING COMPUTITONAL METHOD FOR DRUGGABLE BETA CATENIN INHIBITORY PHYTOCOMPOUND FROM GLYCINE MAX L. SEEDS TO TREAT OVARIAN CANCER. Journal of Population Therapeutics and Clinical Pharmacology, 31(1), 1840–1861. https://doi.org/10.53555/jptcp.v31i1.4143
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Author Biographies
Samra Hafeez
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Punjab, Islamic Republic of Pakistan
Asma Ahmed
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Punjab, Islamic Republic of Pakistan
Maryam Mureed
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Punjab, Islamic Republic of Pakistan
Hamna shahid
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Punjab, Islamic Republic of Pakistan
Afaq Akram
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Punjab, Islamic Republic of Pakistan