Mechanistic exploration of bioactive constituents in Gnetum gnemon for GPCR-related cancer treatment through network pharmacology and molecular docking.
ADME
Cancer
GPCRs
Molecular docking
Network pharmacology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 10 2024
28 10 2024
Historique:
received:
14
07
2023
accepted:
03
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
G Protein-Coupled Receptors (GPCRs) are integral membrane proteins that have gained considerable attention as drug targets, particularly in cancer treatment. In this study, we explored the capacity of bioactive compounds derived from Gnetum gnemon (GG) for the development of of pharmaceuticals targeting GPCRs within the context of cancer therapy. Integrated approach combined network pharmacology and molecular docking to identify and validate the underlying pharmacological mechanisms. We retrieved targets for GG-derived compounds and GPCRs-related cancer from databases. Subsequently, we established a protein-protein interaction (PPI) network by mapping the shared targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to predict the mechanism of action of these targets. Molecular docking was conducted to validate our findings. We identified a total of 265 targets associated with GG-derived bioactive compounds for the treatment of GPCRs-related cancer. Functional enrichment analysis revealed the promising therapeutic effects of these targets on GPCRs-related cancer pathways. The PPI network analysis identified hub targets, including MAPK3, SRC, EGFR, STAT3, ESR1, MTOR, CCND1, and PPARG, which demonstrate as treatment targets for GPCRs-related cancer using GG-derived compounds. Additionally, molecular docking experiments demonstrated the strong binding affinity of gnetin A, gnetin C, (-)-viniferin, and resveratrol dimer, thus inhibiting MAPK3, SRC, EGFR, and MTOR. Survival analysis established the clinical prognostic relevance of identified hub genes in cancer. This study presents a novel approach for comprehending the therapeutic mechanisms of GG-derived active compounds and thereby paving the way for their prospective clinical applications in the field of cancer treatment.
Identifiants
pubmed: 39468096
doi: 10.1038/s41598-024-75240-4
pii: 10.1038/s41598-024-75240-4
doi:
Substances chimiques
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25738Informations de copyright
© 2024. The Author(s).
Références
Sriram, K. & Insel, P. A. GPCRs as targets for approved drugs: how many targets and how many drugs? Mol. Pharmacol. 93, 251–258. https://doi.org/10.1124/mol.117.111062 (2018).
doi: 10.1124/mol.117.111062
pubmed: 29298813
pmcid: 5820538
Thomsen, W., Frazer, J. & Unett, D. Functional assays for screening GPCR targets. Curr. Opin. Biotechnol. 16, 655–665. https://doi.org/10.1016/j.copbio.2005.10.008 (2005).
doi: 10.1016/j.copbio.2005.10.008
pubmed: 16257523
Yang, D. et al. G protein-coupled receptors: structure- and function-based drug discovery. Sig Transduct. Target. Ther. 6, 7. https://doi.org/10.1038/s41392-020-00435-w (2021).
doi: 10.1038/s41392-020-00435-w
Wootten, D., Christopoulos, A., Marti-Solano, M., Babu, M. M. & Sexton, P. M. Mechanisms of signalling and biased agonism in G protein-coupled receptors. Nat. Rev. Mol. Cell. Biol. 19, 638–653. https://doi.org/10.1038/s41580-018-0049-3 (2018).
doi: 10.1038/s41580-018-0049-3
pubmed: 30104700
Chaudhary, P. K. & Kim, S. An insight into GPCR and G-Proteins as Cancer drivers. Cells. 10, 3288. https://doi.org/10.3390/cells10123288 (2021).
doi: 10.3390/cells10123288
pubmed: 34943797
pmcid: 8699078
Gutkind, J. S. The pathways connecting G protein-coupled receptors to the nucleus through divergent mitogen-activated protein kinase cascades. J. Biol. Chem. 273, 1839–1842. https://doi.org/10.1074/jbc.273.4.1839 (1998).
doi: 10.1074/jbc.273.4.1839
pubmed: 9442012
Hemmings, B. A. & Restuccia, D. F. PI3K-PKB/AKT pathway. Cold Spring Harb Perspect. Biol. 4, a011189. https://doi.org/10.1101/cshperspect.a011189 (2012).
doi: 10.1101/cshperspect.a011189
pubmed: 22952397
pmcid: 3428770
Kang, S. Y. et al. Potential of bioactive Food Components against Gastric Cancer: insights into molecular mechanism and therapeutic targets. Cancers. 13, 4502. https://doi.org/10.3390/cancers13184502 (2021).
doi: 10.3390/cancers13184502
pubmed: 34572730
pmcid: 8469857
George, B. P., Chandran, R. & Abrahamse, H. Role of Phytochemicals in Cancer Chemoprevention: Insights. Antioxidants. 10, 1455. (2021). https://doi.org/10.3390/antiox10091455
Anisong, N. et al. A comprehensive review on nutritional contents and functional properties of Gnetum gnemon Linn. Food Sci. Technol. 42, e100121. https://doi.org/10.1590/fst.100121 (2022).
doi: 10.1590/fst.100121
Kato, E., Tokunaga, Y. & Sakan, F. Stilbenoids isolated from the seeds of Melinjo (Gnetum gnemon L.) and their biological activity. J. Agric. Food Chem. 57, 2544–2549. https://doi.org/10.1021/jf803077p (2009).
doi: 10.1021/jf803077p
pubmed: 19222220
Narayanan, N. K., Nargi, D., Randolph, C. & Narayanan, B. A. Liposome encapsulation of gnetin C, a novel resveratrol dimer from Gnetum gnemon, reduces cancer cell proliferation and induces apoptosis. PLoS ONE. 10, e0124807. https://doi.org/10.1371/journal.pone.0124807 (2015).
doi: 10.1371/journal.pone.0124807
Parupathi, P. et al. Gnetin C intercepts MTA1-Associated neoplastic progression in prostate Cancer. Cancers. 14, 6038. https://doi.org/10.3390/cancers14246038 (2022).
doi: 10.3390/cancers14246038
pubmed: 36551523
pmcid: 9775406
Yang, M., Chen, J. L., Xu, L. W. & Ji, G. Navigating traditional Chinese medicine network pharmacology and computational tools. Evid Based Complement Alternat Med. 2013, 731969. https://doi.org/10.1155/2013/731969 (2013).
Hopkins, A. L. & Network Pharmacology Nat. Biotechnol. 25, 1110–1111. https://doi.org/10.1038/nbt1007-1110 (2007).
doi: 10.1038/nbt1007-1110
pubmed: 17921993
Chakraborty, C., Doss, C. G. P., Chen, L. & Zhu, H. Evaluating protein-protein interaction (PPI) networks for diseases pathway, target discovery, and drug-design using ‘in silico pharmacology’. Curr. Protein Pept. Sci. 15, 561–571. https://doi.org/10.2174/1389203715666140724090153 (2014).
doi: 10.2174/1389203715666140724090153
pubmed: 25059326
Macalino, S. J., Gosu, V., Hong, S. & Choi, S. Role of computer-aided drug design in modern drug discovery. Arch. Pharm. Res. 38, 1686–1701. https://doi.org/10.1007/s12272-015-0640-5 (2015).
doi: 10.1007/s12272-015-0640-5
pubmed: 26208641
Pinzi, L. & Rastelli, G. Molecular Docking: shifting paradigms in Drug Discovery. Int. J. Mol. Sci. 20, 4331. https://doi.org/10.3390/ijms20184331 (2019).
doi: 10.3390/ijms20184331
pubmed: 31487867
pmcid: 6769923
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. 7, 42717. https://doi.org/10.1038/srep42717 (2017).
doi: 10.1038/srep42717
pubmed: 28256516
pmcid: 5335600
Daina, A., Michielin, O. & Zoete, V. Swiss target prediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 47, W357–W364. https://doi.org/10.1093/nar/gkz382 (2019).
doi: 10.1093/nar/gkz382
pubmed: 31106366
pmcid: 6602486
Stelzer, G. et al. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinform. 54 1.30.1–1.30.33 (2016).
Ge, S. X., Jung, D. & Yao, R. ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics. 36, 2628–2629. https://doi.org/10.1093/bioinformatics/btz931 (2020).
doi: 10.1093/bioinformatics/btz931
pubmed: 31882993
Szklarczyk, D. et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51, D638–D646. https://doi.org/10.1093/nar/gkac1000 (2023).
doi: 10.1093/nar/gkac1000
pubmed: 36370105
Shannon, P. et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504. https://doi.org/10.1101/gr.1239303 (2003).
doi: 10.1101/gr.1239303
pubmed: 14597658
pmcid: 403769
Tang, Z., Kang, B., Li, C., Chen, T. & Zhang, Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 47, W556–W560. https://doi.org/10.1093/nar/gkz430 (2019).
doi: 10.1093/nar/gkz430
pubmed: 31114875
pmcid: 6602440
Sung, H. et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249. https://doi.org/10.3322/caac.21660 (2021).
doi: 10.3322/caac.21660
pubmed: 33538338
Insel, P. A. et al. GPCRomics: GPCR expression in Cancer cells and tumors identifies New, potential biomarkers and therapeutic targets. Front. Pharmacol. 9, 431. https://doi.org/10.3389/fphar.2018.00431 (2018).
doi: 10.3389/fphar.2018.00431
pubmed: 29872392
pmcid: 5972277
Shi, X., Gangadharan, B., Brass, L. F., Ruf, W. & Mueller, B. M. Protease-activated receptors (PAR1 and PAR2) contribute to tumor cell motility and metastasis. Mol. Cancer Res. 2, 395–402 (2004).
doi: 10.1158/1541-7786.395.2.7
pubmed: 15280447
Kandoth, C. et al. Mutational landscape and significance across 12 major cancer types. Nature. 502, 333–339. https://doi.org/10.1038/nature12634 (2013).
doi: 10.1038/nature12634
pubmed: 24132290
pmcid: 3927368
Su, L. D., Peng, J. M. & Ge, Y. B. Formyl peptide receptor 2 mediated chemotherapeutics drug resistance in colon cancer cells. Eur. Rev. Med. Pharmacol. Sci. 22, 95–100. https://doi.org/10.26355/eurrev_201801_14105 (2018).
doi: 10.26355/eurrev_201801_14105
pubmed: 29364475
Usman, S., Khawer, M., Rafique, S., Naz, Z. & Saleem, K. The current status of anti-GPCR drugs against different cancers. J. Pharm. Anal. 10, 517–521. https://doi.org/10.1016/j.jpha.2020.01.001 (2020).
doi: 10.1016/j.jpha.2020.01.001
pubmed: 33425448
pmcid: 7775845
Wang, Y. et al. Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res. 48, 1031–1041. https://doi.org/10.1093/nar/gkz981 (2020).
doi: 10.1093/nar/gkz981
Derakhshani, A. et al. From Oncogenic Signaling pathways to single-cell sequencing of Immune cells: changing the Landscape of Cancer Immunotherapy. Molecules. 26, 2278. https://doi.org/10.3390/molecules26082278 (2021).
doi: 10.3390/molecules26082278
pubmed: 33920054
pmcid: 8071039
Rascio, F. et al. The pathogenic role of PI3K/AKT pathway in Cancer Onset and Drug Resistance: an updated review. Cancers. 13, 3949. https://doi.org/10.3390/cancers13163949 (2021).
doi: 10.3390/cancers13163949
pubmed: 34439105
pmcid: 8394096
Smolarz, B., Durczyński, A., Romanowicz, H., Szyłło, K. & Hogendorf, P. miRNAs in Cancer. Int. J. Mol. Sci. 23, 2805. https://doi.org/10.3390/ijms23052805 (2022).
doi: 10.3390/ijms23052805
pubmed: 35269947
pmcid: 8910953
Cao, H. Y. et al. MiR-129 reduces CDDP resistance in gastric cancer cells by inhibiting MAPK3. Eur. Rev. Med. Pharmacol. 24, 11468. https://doi.org/10.26355/eurrev_202011_23759 (2020).
doi: 10.26355/eurrev_202011_23759
Pelaz, S. G. & Tabernero, A. Src: coordinating metabolism in cancer. Oncogene. 41, 4917–4928. https://doi.org/10.1038/s41388-022-02487-4 (2022).
doi: 10.1038/s41388-022-02487-4
pubmed: 36217026
pmcid: 9630107
Jiang, T. & Qiu, Y. Interaction between Src and a C-terminal proline-rich motif of akt is required for akt activation. J. Biol. Chem. 278, 15789–15793. https://doi.org/10.1074/jbc.M212525200 (2003).
doi: 10.1074/jbc.M212525200
pubmed: 12600984
Uribe, M. L., Marrocco, I. & Yarden, Y. EGFR in Cancer: signaling mechanisms, drugs, and Acquired Resistance. Cancers. 13, 2748. https://doi.org/10.3390/cancers13112748 (2021).
doi: 10.3390/cancers13112748
pubmed: 34206026
pmcid: 8197917
Stark, G. R. & &Darnell, J. J. The JAK-STAT pathway at twenty. Immunity. 36, 503–514. https://doi.org/10.1016/j.immuni.2012.03.013 (2012).
doi: 10.1016/j.immuni.2012.03.013
pubmed: 22520844
pmcid: 3909993
Groner, B. & von Manstein, V. Jak Stat signaling and cancer: opportunities, benefits and side effects of targeted inhibition. Mol. Cell. Endocrinol. 451, 1–14. https://doi.org/10.1016/j.mce.2017.05.033 (2017).
doi: 10.1016/j.mce.2017.05.033
pubmed: 28576744
Wang, H. Q. et al. STAT3 pathway in cancers: past, present, and future. Med. Comm. 3, e124. https://doi.org/10.1002/mco2.124 (2020).
doi: 10.1002/mco2.124
Hua, H. et al. Mechanisms for estrogen receptor expression in human cancer. Exp. Hematol. Oncol. 7, 24. https://doi.org/10.1186/s40164-018-0116-7 (2018).
doi: 10.1186/s40164-018-0116-7
pubmed: 30250760
pmcid: 6148803
Tian, T., Li, X. & Zhang, J. mTOR Signaling in Cancer and mTOR inhibitors in solid Tumor Targeting Therapy. Int. J. Mol. Sci. 20, 755. https://doi.org/10.3390/ijms20030755 (2019).
doi: 10.3390/ijms20030755
pubmed: 30754640
pmcid: 6387042
Chen, S. & Li, L. Degradation strategy of cyclin D1 in cancer cells and the potential clinical application. Front. Oncol. 12, 949688. https://doi.org/10.3389/fonc.2022.949688 (2022).
doi: 10.3389/fonc.2022.949688
pubmed: 36059670
pmcid: 9434365
Tan, Y. et al. PPAR-α modulators as current and potential Cancer treatments. Front. Oncol. 11, 707. https://doi.org/10.3389/fonc.2021.599995 (2021).
doi: 10.3389/fonc.2021.599995
Opferman, J. T., Kothari, A. & Anti-apoptotic BCL-2 family members in development. Cell. Death Differ. 25, 37–45. https://doi.org/10.1038/cdd.2017.170 (2018).
doi: 10.1038/cdd.2017.170
pubmed: 29099482
Benelli, R., Venè, R. & Ferrari, N. Prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2), a complex target for colorectal cancer prevention and therapy. Transl Res. 196, 42–61. https://doi.org/10.1016/j.trsl.2018.01.003 (2018).
doi: 10.1016/j.trsl.2018.01.003
pubmed: 29421522
Kim, J. H. et al. Cytotoxic and Antimutagenic Stilbenes from seeds of Paeonia lactiflora. Arch. Pharm. Res. 25, 293–299. https://doi.org/10.1007/BF02976629 (2002).
doi: 10.1007/BF02976629
pubmed: 12135100
Muhtadi Hakim, E. H. et al. Cytotoxic resveratrol oligomers from the Tree Bark of Dipterocarpus Hasseltii. Fitoterapia. 77, 550–555. https://doi.org/10.1016/j.fitote.2006.07.004 (2006).
doi: 10.1016/j.fitote.2006.07.004
pubmed: 17071016
Tian, X. et al. Chemical characterization of Main Bioactive constituents in Paeonia Ostii seed meal and GC-MS analysis of seed oil. J. Food Biochem. 44, e13088. https://doi.org/10.1111/jfbc.13088 (2020).
doi: 10.1111/jfbc.13088
pubmed: 31646682
Huang, C. et al. ε-Viniferin and α-viniferin alone or in combination induced apoptosis and necrosis in osteosarcoma and non-small cell lung cancer cells. Food Chem. Toxicol. 158, 112617. https://doi.org/10.1016/j.fct.2021.112617 (2021).
doi: 10.1016/j.fct.2021.112617
pubmed: 34728247
Colin, D. et al. Antiproliferative activities of resveratrol and related compounds in human hepatocyte derived HepG2 cells are associated with biochemical cell disturbance revealed by fluorescence analyses. Biochimie. 90, 1674–1684. https://doi.org/10.1016/j.biochi.2008.06.006 (2008).
doi: 10.1016/j.biochi.2008.06.006
pubmed: 18627786
Nivelle, L. et al. Molecular analysis of differential antiproliferative activity of resveratrol, epsilon viniferin and labruscol on melanoma cells and normal dermal cells. Food Chem. Toxicol. 116, 323–334. https://doi.org/10.1016/j.fct.2018.04.043 (2018).
doi: 10.1016/j.fct.2018.04.043
pubmed: 29684496
Chiou, W. C. et al. α-Viniferin and ε-Viniferin inhibited TGF-β1-Induced epithelial-mesenchymal transition, Migration and Invasion in Lung Cancer cells through downregulation of Vimentin expression. Nutrients. 14, 2294. https://doi.org/10.3390/nu14112294 (2022).
doi: 10.3390/nu14112294
pubmed: 35684095
pmcid: 9182810
Hsu, P. C., Yang, C. T., Jablons, D. M. & You, L. The crosstalk between Src and Hippo/YAP Signaling Pathways in Non-small Cell Lung Cancer (NSCLC). Cancers. 12 1361. https://doi.org/10.3390/cancers12061361 (2020).
doi: 10.3390/cancers12061361
pubmed: 32466572
pmcid: 7352956
Shen, J. et al. Update on Phytochemistry and Pharmacology of naturally occurring Resveratrol oligomers. Molecules. 22, 2050. https://doi.org/10.3390/molecules22122050 (2017).
doi: 10.3390/molecules22122050
pubmed: 29186764
pmcid: 6149893
Koushki, M. et al. A miraculous natural compound for diseases treatment. Food Sci. Nutr. 6, 2473–2490. https://doi.org/10.1002/fsn3.855 (2018).
doi: 10.1002/fsn3.855
pubmed: 30510749
pmcid: 6261232
Xue, Y. Q. et al. Resveratrol oligomers for the prevention and treatment of cancers. Oxid. Med. Cell Longev. 2014, 765832. https://doi.org/10.1155/2014/765832 (2014).
Narayanan, N. K. et al. Antitumor activity of melinjo (Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in a colon26 tumor-bearing mouse model in vivo. Cancer Med. 4, 1767–1780. https://doi.org/10.1002/cam4.520 (2015).
doi: 10.1002/cam4.520
pubmed: 26408414
pmcid: 4674003
Espinoza, J. L. et al. The simultaneous inhibition of the mTOR and MAPK pathways with Gnetin-C induces apoptosis in acute myeloid leukemia. Cancer Lett. 400, 127–136. https://doi.org/10.1016/j.canlet.2017.04.027 (2017).
doi: 10.1016/j.canlet.2017.04.027
pubmed: 28456658
Breems, D. A. et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J. Clin. Oncol. 26, 4791–4797. https://doi.org/10.1200/JCO.2008.16.0259 (2008).
doi: 10.1200/JCO.2008.16.0259
pubmed: 18695255
Espinoza, J. L. & Inaoka, P. T. Gnetin-C and other resveratrol oligomers with cancer chemopreventive potential. Ann. N Y Acad. Sci. 1403, 5–14. https://doi.org/10.1111/nyas.13450 (2017).
doi: 10.1111/nyas.13450
pubmed: 28856688
Steelman, L. S. et al. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging. 3, 192–222. https://doi.org/10.18632/aging.100296 (2011).
doi: 10.18632/aging.100296
pubmed: 21422497
pmcid: 3091517
Ikeda, E. et al. Healing effects of monomer and dimer resveratrol in a mouse periodontitis model. BMC Oral Health. 22, 460. https://doi.org/10.1186/s12903-022-02499-2 (2022).
doi: 10.1186/s12903-022-02499-2
pubmed: 36319994
pmcid: 9623911
Kumar, A., Dholakia, K., Sikorska, G., Martinez, L. A. & Levenson, A. S. MTA1-Dependent anticancer activity of gnetin C in prostate Cancer. Nutrients. 11, 2096. https://doi.org/10.3390/nu11092096 (2019).
doi: 10.3390/nu11092096
pubmed: 31487842
pmcid: 6770780
Dias, S. J. et al. Nuclear MTA1 overexpression is associated with aggressive prostate cancer, recurrence and metastasis in African americans. Sci. Rep. 3, 2331. https://doi.org/10.1038/srep02331 (2013).
doi: 10.1038/srep02331
pubmed: 23900262
pmcid: 3728596
Dhar, S. et al. Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer. Oncotarget. 7, 18469–18484. https://doi.org/10.18632/oncotarget.7841 (2016).
doi: 10.18632/oncotarget.7841
pubmed: 26943043
pmcid: 4951302
Gadkari, K. et al. Therapeutic potential of gnetin C in prostate Cancer: a pre-clinical study. Nutrients. 12, 3631. https://doi.org/10.3390/nu12123631 (2020).
doi: 10.3390/nu12123631
pubmed: 33255879
pmcid: 7760540
Nakagami, Y. et al.. Immunomodulatory and metabolic changes after Gnetin-C supplementation in humans. Nutrients. 11, 1403. https://doi.org/10.3390/nu11061403 (2019).
doi: 10.3390/nu11061403
pubmed: 31234376
pmcid: 6628299
Tani, H. et al. Pharmacokinetics and safety of resveratrol derivatives in humans after oral administration of melinjo (Gnetum gnemon L.) seed extract powder. J. Agric. Food Chem. 62, 1999–2007. https://doi.org/10.1021/jf4048435 (2014).
doi: 10.1021/jf4048435
pubmed: 24495149
Ota, H. et al. Trans-resveratrol in Gnetum gnemon protects against oxidative-stress-induced endothelial senescence. J. Nat. Prod. 76, 1242–1247. https://doi.org/10.1021/np300841v (2013).
doi: 10.1021/np300841v
pubmed: 23859249
Liu, R. et al. ε-Viniferin, a promising natural oligostilbene, ameliorates hyperglycemia and hyperlipidemia by activating AMPK in vivo. Food Funct. 11, 10084–10093. https://doi.org/10.1039/d0fo01932a (2020).
doi: 10.1039/d0fo01932a
pubmed: 33140813
Triputra, M. A. & Yanuar, A. Analysis of compounds isolated from Gnetum gnemon L. Seeds as potential ACE inhibitors through Molecular Docking and Molecular Dynamics simulations. J. Young Pharm. 10, 32–39. https://doi.org/10.5530/jyp.2018.2s.7 (2018).
doi: 10.5530/jyp.2018.2s.7
Dewi, I. G. A. I. P., Yuda, P. E. S. K. & Rahadi, I. W. S. Silico Study and Pharmacokinetics Prediction of ɛ-Vinicompoundmpound as Anticancercandidatedidate. Jrki. 13, 121–130 (2023).
Romadhona, K. N., Shifa, N. A., Asmiyenti, D. & Djalil, A. D. Molecular Docking of Gnetin C and Trans-resveratrol of Melinjo Seeds (Gnetum Gnemon L.) Used as the Inhibitors of Breast Cancer Cells MCF-7. IJHMS. 4, 58–63.
Savitri, R. I., Arifin, N. H. & Febriansah, R. Antioxidant, cytotoxic activity and protein target inhibition of Ethyl acetate Fraction Melinjo seed (Gnetum gnemon L.) by in Vitro and in Silico studies on HeLa cervical Cancer cells. HAYATI J. Biosci. 30, 864–873. https://doi.org/10.4308/hjb.30.5.864-873 (2023).
doi: 10.4308/hjb.30.5.864-873
Hsu, L. H., Chu, N. M., Kao, S. H. & Estrogen Estrogen receptor and Lung Cancer. Int. J. Mol. Sci. 18, 1713. https://doi.org/10.3390/ijms18081713 (2017).
doi: 10.3390/ijms18081713
pubmed: 28783064
pmcid: 5578103
Kay, C. et al. Current trends in the treatment of HR+/HER2 + breast cancer. Future Oncol. 17, 1665–1681. https://doi.org/10.2217/fon-2020-0504 (2021).
doi: 10.2217/fon-2020-0504
pubmed: 33726508
New, D. C. & Wong, Y. H. Molecular mechanisms mediating the G protein-coupled receptor regulation of cell cycle progression. J. Mol. Signal. 26, 2. https://doi.org/10.1186/1750-2187-2-2 (2007).
doi: 10.1186/1750-2187-2-2
Luttrell, D. K. & Luttrell, L. M. Not so strange bedfellows: G-protein-coupled receptors and Src family kinases. Oncogene. 23, 7969–7978. https://doi.org/10.1038/sj.onc.1208162 (2004).
doi: 10.1038/sj.onc.1208162
pubmed: 15489914
Ram, P. & Iyengar, R. G protein coupled receptor signaling through the Src and Stat3 pathway: role in proliferation and transformation. Oncogene. 20, 1601–1606. https://doi.org/10.1038/sj.onc.1204186 (2001).
doi: 10.1038/sj.onc.1204186
pubmed: 11313907
Yu, H. et al. Revisiting STAT3 signaling in cancer: new and unexpected biological functions. Nat. Rev. Cancer. 14, 736–746. https://doi.org/10.1038/nrc3818 (2014).
doi: 10.1038/nrc3818
pubmed: 25342631
Magaway, C., Kim, E. & Jacinto, E. Targeting mTOR and metabolism in Cancer: lessons and innovations. Cells. 8, 1584. https://doi.org/10.3390/cells8121584 (2019).
doi: 10.3390/cells8121584
pubmed: 31817676
pmcid: 6952948
Kim, S. et al. PubChem 2023 update. Nucleic Acids Res. 51, D1373–D1380. https://doi.org/10.1093/nar/gkac956 (2023).
doi: 10.1093/nar/gkac956
pubmed: 36305812
Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612. https://doi.org/10.1002/jcc.20084 (2004).
doi: 10.1002/jcc.20084
pubmed: 15264254
Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235–242. https://doi.org/10.1093/nar/28.1.235 (2000).
doi: 10.1093/nar/28.1.235
pubmed: 10592235
pmcid: 102472
Eberhardt, J., Santos-Martins, D., F Tillack, A. & Forli, S. AutoDock Vina 1.2.0: new docking methods, expanded force field, and Python Bindings. J. Chem. Inf. Model. 61, 3891–3898. https://doi.org/10.1021/acs.jcim.1c00203 (2021).
doi: 10.1021/acs.jcim.1c00203
pubmed: 34278794
pmcid: 10683950
Sama-Ae, I., Pattaranggoon, N. C. & Tedasen, A. In silico prediction of Antifungal compounds from Natural sources towards Lanosterol 14-alpha demethylase (CYP51) using Molecular docking and Molecular dynamic simulation. J. Mol. Graph. Model. 121, 108435. https://doi.org/10.1016/j.jmgm.2023.108435 (2023).