Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 Feb 2024
06 Feb 2024
Historique:
received:
03
10
2023
accepted:
09
01
2024
medline:
7
2
2024
pubmed:
7
2
2024
entrez:
6
2
2024
Statut:
epublish
Résumé
Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways.
Identifiants
pubmed: 38321096
doi: 10.1038/s41598-024-51804-2
pii: 10.1038/s41598-024-51804-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3043Subventions
Organisme : European- Union
ID : LX22NPO5102 and LX22NPO5107
Organisme : European- Union
ID : LX22NPO5102 and LX22NPO5107
Organisme : European- Union
ID : LX22NPO5102 and LX22NPO5107
Organisme : Charles University
ID : SVV260637; SVV260521; UNCE 204064; Progres LF1 Q38 and Q27, Cooperatio ONCO
Organisme : Ministry of Education, Youth, and Sports
ID : . LM2023053
Organisme : Technology Agency of the Czech Republic
ID : TN02000109
Organisme : the Ministry of Health
ID : NU22-D-136 and NU21-08-00407
Informations de copyright
© 2024. The Author(s).
Références
Abramenko, N. et al. Estrogen receptor modulators in viral infections such as sars-cov-2: Therapeutic consequences. Int. J. Mol. Sci. 22(12), 6551 (2021).
pubmed: 34207220
pmcid: 8233910
doi: 10.3390/ijms22126551
Breithaupt-Faloppa, A. C. et al. 17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection. Clinics (Sao Paulo) 75, e1980 (2020).
pubmed: 32490931
doi: 10.6061/clinics/2020/e1980
Millas, I. & Duarte Barros, M. Estrogen receptors and their roles in the immune and respiratory systems. Anat. Rec. 304(6), 1185–1193 (2021).
doi: 10.1002/ar.24612
Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16(10), 626–638 (2016).
pubmed: 27546235
doi: 10.1038/nri.2016.90
Brábek, J. et al. Interleukin-6: Molecule in the intersection of cancer, ageing and COVID-19. Int. J. Mol. Sci. 21(21), 7937 (2020).
pubmed: 33114676
pmcid: 7662856
doi: 10.3390/ijms21217937
Kaňuchová, M. et al. Genistein does not inhibit TGF-beta1-induced conversion of human dermal fibroblasts to myofibroblasts. Physiol. Res. 70(5), 815–820 (2021).
pubmed: 34505520
pmcid: 8820530
doi: 10.33549/physiolres.934666
Lathigara, D., Kaushal, D. & Wilson, R. B. Molecular mechanisms of western diet-induced obesity and obesity-related carcinogenesis—A narrative review. Metabolites 13(5), 675 (2023).
pubmed: 37233716
pmcid: 10222258
doi: 10.3390/metabo13050675
Gál, P. et al. Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: Critical role of inflammation. Histochem. Cell. Biol. 158(5), 415–434 (2022).
pubmed: 35867145
pmcid: 9305064
doi: 10.1007/s00418-022-02140-x
Fife, B. T. & Bluestone, J. A. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol. Rev. 224, 166–182 (2008).
pubmed: 18759926
doi: 10.1111/j.1600-065X.2008.00662.x
Buchbinder, E. I. & Desai, A. CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. Am. J. Clin. Oncol. 39(1), 98–106 (2016).
pubmed: 26558876
pmcid: 4892769
doi: 10.1097/COC.0000000000000239
Rotte, A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J. Exp. Clin. Cancer Res. 38(1), 255 (2019).
pubmed: 31196207
pmcid: 6567914
doi: 10.1186/s13046-019-1259-z
Okazaki, T. & Honjo, T. PD-1 and PD-1 ligands: From discovery to clinical application. Int. Immunol. 19(7), 813–824 (2007).
pubmed: 17606980
doi: 10.1093/intimm/dxm057
Chemnitz, J. M. et al. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol. 173(2), 945–954 (2004).
pubmed: 15240681
doi: 10.4049/jimmunol.173.2.945
Laba, S., Mallett, G. & Amarnath, S. The depths of PD-1 function within the tumor microenvironment beyond CD8(+) T cells. Semin. Cancer Biol. 86(Pt 2), 1045–1055 (2022).
pubmed: 34048897
doi: 10.1016/j.semcancer.2021.05.022
Celis-Gutierrez, J. et al. Quantitative interactomics in primary T cells provides a rationale for concomitant PD-1 and BTLA coinhibitor blockade in cancer immunotherapy. Cell Rep. 27(11), 3315-3330.e7 (2019).
pubmed: 31189114
pmcid: 6581740
doi: 10.1016/j.celrep.2019.05.041
Concha-Benavente, F. et al. Identification of the cell-intrinsic and -extrinsic pathways downstream of EGFR and IFNγ that induce PD-L1 Expression in head and neck cancer. Cancer Res. 76(5), 1031–1043 (2016).
pubmed: 26676749
doi: 10.1158/0008-5472.CAN-15-2001
Pandey, P. et al. Review to understand the crosstalk between immunotherapy and tumor metabolism. Molecules 28(2), 862 (2023).
pubmed: 36677919
pmcid: 9863813
doi: 10.3390/molecules28020862
Lin, X. et al. Progress in PD-1/PD-L1 pathway inhibitors: From biomacromolecules to small molecules. Eur. J. Med. Chem. 186, 111876 (2020).
pubmed: 31761384
doi: 10.1016/j.ejmech.2019.111876
Wu, X. et al. Insights into non-peptide small-molecule inhibitors of the PD-1/PD-L1 interaction: Development and perspective. Bioorg. Med. Chem. 33, 116038 (2021).
pubmed: 33517226
doi: 10.1016/j.bmc.2021.116038
Smith, W. M. et al. Therapeutic targeting of immune checkpoints with small molecule inhibitors. Am. J. Transl. Res. 11(2), 529–541 (2019).
pubmed: 30899360
pmcid: 6413273
Li, W. et al. Immune checkpoint PD-1/PD-L1 CTLA-4/CD80 are blocked by Rhus Verniciflua stokes and its active compounds. Molecules 24(22), 4062 (2019).
pubmed: 31717574
pmcid: 6891444
doi: 10.3390/molecules24224062
Jing, L. et al. Quercetin inhibiting the PD-1/PD-L1 interaction for immune-enhancing cancer chemopreventive agent. Phytother. Res. 35(11), 6441–6451 (2021).
pubmed: 34560814
doi: 10.1002/ptr.7297
Kim, J. H. et al. Kaempferol and its glycoside, Kaempferol 7-O-rhamnoside, inhibit PD-1/PD-L1 interaction in vitro. Int. J. Mol. Sci. 21(9), 3239 (2020).
pubmed: 32375257
pmcid: 7247329
doi: 10.3390/ijms21093239
Bajusz, D., Rácz, A. & Héberger, K. Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations?. J. Cheminf. 7(1), 20 (2015).
doi: 10.1186/s13321-015-0069-3
Trott, O. & Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31(2), 455–461 (2010).
pubmed: 19499576
pmcid: 3041641
doi: 10.1002/jcc.21334
Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28(1), 235–242 (2000).
pubmed: 10592235
pmcid: 102472
doi: 10.1093/nar/28.1.235
Collins, A. V. et al. The interaction properties of costimulatory molecules revisited. Immunity 17(2), 201–210 (2002).
pubmed: 12196291
doi: 10.1016/S1074-7613(02)00362-X
Chen, W. et al. Strategies for developing PD-1 inhibitors and future directions. Biochem. Pharmacol. 202, 115113 (2022).
pubmed: 35640711
doi: 10.1016/j.bcp.2022.115113
Park, J.-J. et al. Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1. Nat. Commun. 12(1), 1222 (2021).
pubmed: 33619272
pmcid: 7900207
doi: 10.1038/s41467-021-21410-1
Dong, Y., Sun, Q. & Zhang, X. PD-1 and its ligands are important immune checkpoints in cancer. Oncotarget 8(2), 2171–2186 (2017).
pubmed: 27974689
doi: 10.18632/oncotarget.13895
Brooks, B. et al. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4, 187–217 (2004).
doi: 10.1002/jcc.540040211
Jo, S. et al. CHARMM-GUI: A web-based graphical user interface for CHARMM. J. Comput. Chem. 29(11), 1859–1865 (2008).
pubmed: 18351591
doi: 10.1002/jcc.20945
Alifu, M. et al. Checkpoint inhibitors as dual immunotherapy in advanced non-small cell lung cancer: A meta-analysis. Front. Oncol. 13, 1146905 (2023).
pubmed: 37397392
pmcid: 10311062
doi: 10.3389/fonc.2023.1146905
Wu, K. et al. The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: A meta-analysis. Exp. Hematol. Oncol. 8, 26 (2019).
pubmed: 31673481
pmcid: 6815037
doi: 10.1186/s40164-019-0150-0
Mahmud, A. R. et al. Natural flavonols: Actions, mechanisms, and potential therapeutic utility for various diseases. Beni Suef Univ. J. Basic Appl. Sci. 12(1), 47 (2023).
pubmed: 37216013
pmcid: 10183303
doi: 10.1186/s43088-023-00387-4
Agency, E.M., Assessment Report for Conbriza. 2009. p. 46.
Sidhu, A. et al. Effect of quinestrol on body weight, vital organs, biochemicals and genotoxicity in adult male lesser bandicoot rat, Bandicota bengalensis. Pestic Biochem. Physiol. 165, 104544 (2020).
pubmed: 32359538
doi: 10.1016/j.pestbp.2020.02.010
Aitken, D. A. & Daw, E. G. Allergic reaction to quinestrol. Br. Med. J. 2(5702), 177 (1970).
pubmed: 5443982
pmcid: 1699992
doi: 10.1136/bmj.2.5702.177-a
Tong, D. Selective estrogen receptor modulators contribute to prostate cancer treatment by regulating the tumor immune microenvironment. J. Immunother. Cancer 10(4), e002944 (2022).
pubmed: 35383112
pmcid: 8984050
doi: 10.1136/jitc-2021-002944
Segovia-Mendoza, M. & Morales-Montor, J. Immune tumor microenvironment in breast cancer and the participation of estrogen and its receptors in cancer physiopathology. Front. Immunol. 10, 348 (2019).
pubmed: 30881360
pmcid: 6407672
doi: 10.3389/fimmu.2019.00348
Zhang, N. et al. The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer. Int. J. Oncol. 49(4), 1360–1368 (2016).
pubmed: 27499357
doi: 10.3892/ijo.2016.3632
Tan, X. et al. Mechanisms of Quercetin against atrial fibrillation explored by network pharmacology combined with molecular docking and experimental validation. Sci. Rep. 12(1), 9777 (2022).
pubmed: 35697725
pmcid: 9192746
doi: 10.1038/s41598-022-13911-w
Hering, N. A. et al. Targeting interleukin-6/glycoprotein-130 signaling by raloxifene or SC144 enhances paclitaxel efficacy in pancreatic cancer. Cancers (Basel) 15(2), 456 (2023).
pubmed: 36672405
doi: 10.3390/cancers15020456
Maennling, A. E. et al. Molecular targeting therapy against EGFR family in breast cancer: Progress and future potentials. Cancers (Basel) 11(12), 1826 (2019).
pubmed: 31756933
doi: 10.3390/cancers11121826
Frawley, T. & Piskareva, O. Extracellular vesicle dissemination of epidermal growth factor receptor and ligands and its role in cancer progression. Cancers (Basel) 12(11), 3200 (2020).
pubmed: 33143170
doi: 10.3390/cancers12113200
Peles, E. & Yarden, Y. Neu and its ligands: From an oncogene to neural factors. Bioessays 15(12), 815–824 (1993).
pubmed: 7908191
doi: 10.1002/bies.950151207
Wieduwilt, M. J. & Moasser, M. M. The epidermal growth factor receptor family: Biology driving targeted therapeutics. Cell. Mol. Life Sci. 65(10), 1566–1584 (2008).
pubmed: 18259690
pmcid: 3060045
doi: 10.1007/s00018-008-7440-8
Li, C. W. et al. Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nat. Commun. 7, 12632 (2016).
pubmed: 27572267
pmcid: 5013604
doi: 10.1038/ncomms12632
Hsu, J. M. et al. Posttranslational modifications of PD-L1 and their applications in cancer therapy. Cancer Res. 78(22), 6349–6353 (2018).
pubmed: 30442814
pmcid: 6242346
doi: 10.1158/0008-5472.CAN-18-1892
Lastwika, K. J. et al. Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer. Cancer Res. 76(2), 227–238 (2016).
pubmed: 26637667
doi: 10.1158/0008-5472.CAN-14-3362
Lin, K. et al. EGFR-TKI down-regulates PD-L1 in EGFR mutant NSCLC through inhibiting NF-κB. Biochem. Biophys. Res. Commun. 463(1–2), 95–101 (2015).
pubmed: 25998384
doi: 10.1016/j.bbrc.2015.05.030
Li, X. et al. Interactions between EGFR and PD-1/PD-L1 pathway: Implications for treatment of NSCLC. Cancer Lett. 418, 1–9 (2018).
pubmed: 29309815
doi: 10.1016/j.canlet.2018.01.005
Lee, B. S. et al. Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma. Biochem. Biophys. Res. Commun. 491(2), 493–499 (2017).
pubmed: 28684311
doi: 10.1016/j.bbrc.2017.07.007
To, K. K. W., Fong, W. & Cho, W. C. S. Immunotherapy in treating EGFR-mutant lung cancer: Current challenges and new strategies. Front. Oncol. 11, 635007 (2021).
pubmed: 34113560
pmcid: 8185359
doi: 10.3389/fonc.2021.635007
Wölfle, S. J. et al. PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur. J. Immunol. 41(2), 413–424 (2011).
pubmed: 21268011
doi: 10.1002/eji.201040979
Koopmans, I. et al. A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint. Oncoimmunology 7(8), e1466016 (2018).
pubmed: 30221065
pmcid: 6136863
doi: 10.1080/2162402X.2018.1466016
Mohan, N. et al. Comparative characterization of different molecular formats of bispecific antibodies targeting EGFR and PD-L1. Pharmaceutics 14(7), 1381 (2022).
pubmed: 35890277
pmcid: 9325241
doi: 10.3390/pharmaceutics14071381
Chen, M. et al. Insluin and epithelial growth factor (EGF) promote programmed death ligand 1(PD-L1) production and transport in colon cancer stem cells. BMC Cancer 19(1), 153 (2019).
pubmed: 30770752
pmcid: 6377751
doi: 10.1186/s12885-019-5364-3
Akbay, E. A. et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 3(12), 1355–1363 (2013).
pubmed: 24078774
doi: 10.1158/2159-8290.CD-13-0310
Božović, A. et al. Estrogen receptor beta: The promising biomarker and potential target in metastases. Int. J. Mol. Sci. 22(4), 1656 (2021).
pubmed: 33562134
pmcid: 7914503
doi: 10.3390/ijms22041656
Porras, L., Ismail, H. & Mader, S. Positive regulation of estrogen receptor alpha in breast tumorigenesis. Cells 10(11), 2966 (2021).
pubmed: 34831189
pmcid: 8616513
doi: 10.3390/cells10112966
Hanstein, B. et al. Insights into the molecular biology of the estrogen receptor define novel therapeutic targets for breast cancer. Eur. J. Endocrinol. 150(3), 243–255 (2004).
pubmed: 15012607
doi: 10.1530/eje.0.1500243
Azuma, K. et al. Association of estrogen receptor alpha and histone deacetylase 6 causes rapid deacetylation of tubulin in breast cancer cells. Cancer Res. 69(7), 2935–2940 (2009).
pubmed: 19318565
doi: 10.1158/0008-5472.CAN-08-3458
Lai, J. S. et al. Metastases of prostate cancer express estrogen receptor-beta. Urology 64(4), 814–820 (2004).
pubmed: 15491740
doi: 10.1016/j.urology.2004.05.036
Steiner, M. S. & Raghow, S. Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk. World J. Urol. 21(1), 31–36 (2003).
pubmed: 12756492
doi: 10.1007/s00345-002-0316-x
Fan, P. & Jordan, V. C. Estrogen receptor and the unfolded protein response: Double-edged swords in therapy for estrogen receptor-positive breast cancer. Target Oncol. 17(2), 111–124 (2022).
pubmed: 35290592
pmcid: 9007905
doi: 10.1007/s11523-022-00870-5
Diaz-Ruano, A. B. et al. Estradiol and estrone have different biological functions to induce NF-κB-driven inflammation, EMT and stemness in ER+ cancer cells. Int. J. Mol. Sci. 24(2), 1221 (2023).
pubmed: 36674737
pmcid: 9865376
doi: 10.3390/ijms24021221
Yang, L. et al. Posttranscriptional control of PD-L1 expression by 17β-estradiol via PI3K/Akt signaling pathway in ERα-positive cancer cell lines. Int. J. Gynecol. Cancer 27(2), 196–205 (2017).
pubmed: 27870715
pmcid: 5258765
doi: 10.1097/IGC.0000000000000875
Nilsson, N. & Carlsten, H. Estrogen induces suppression of natural killer cell cytotoxicity and augmentation of polyclonal B cell activation. Cell. Immunol. 158(1), 131–139 (1994).
pubmed: 8087860
doi: 10.1006/cimm.1994.1262
Vegeto, E. et al. Regulation of the lipopolysaccharide signal transduction pathway by 17beta-estradiol in macrophage cells. J. Steroid Biochem. Mol. Biol. 91(1–2), 59–66 (2004).
pubmed: 15261308
doi: 10.1016/j.jsbmb.2004.02.004
Polanczyk, M. J. et al. Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1). Int. Immunol. 19(3), 337–343 (2007).
pubmed: 17267414
doi: 10.1093/intimm/dxl151
Hernandez, S. et al. Differential spatial gene and protein expression associated with recurrence following chemoradiation for localized anal squamous cell cancer. Cancers (Basel) 15(6), 1701 (2023).
pubmed: 36980587
doi: 10.3390/cancers15061701
Zhang, Z. et al. Sema4D silencing increases the sensitivity of nivolumab to B16–F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway. PeerJ 11, e15172 (2023).
pubmed: 37096066
pmcid: 10122458
doi: 10.7717/peerj.15172
Mehra, S. et al. Remodeling of stromal immune microenvironment by urolithin A improves survival with immune checkpoint blockade in pancreatic cancer. Cancer Res. Commun. 3(7), 1224–1236 (2023).
pubmed: 37448553
pmcid: 10337606
doi: 10.1158/2767-9764.CRC-22-0329
Okita, R. et al. PD-L1 overexpression is partially regulated by EGFR/HER2 signaling and associated with poor prognosis in patients with non-small-cell lung cancer. Cancer Immunol. Immunother. 66(7), 865–876 (2017).
pubmed: 28341875
doi: 10.1007/s00262-017-1986-y
Zerdes, I. et al. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: Biology and clinical correlations. Oncogene 37(34), 4639–4661 (2018).
pubmed: 29765155
pmcid: 6107481
doi: 10.1038/s41388-018-0303-3
Rašková, M. et al. The role of IL-6 in cancer cell invasiveness and metastasis-overview and therapeutic opportunities. Cells 11(22), 3698 (2022).
pubmed: 36429126
pmcid: 9688109
doi: 10.3390/cells11223698
Wang, R. et al. S100a9 deficiency accelerates MDS-associated tumor escape via PD-1/PD-L1 overexpression. Acta Biochim. Biophys. Sin. (Shanghai) 55(2), 194–201 (2023).
pubmed: 36810783
doi: 10.3724/abbs.2023015
Li, J. et al. PD-1(+) mast cell enhanced by PD-1 blocking therapy associated with resistance to immunotherapy. Cancer Immunol. Immunother. 72(3), 633–645 (2023).
pubmed: 36018370
doi: 10.1007/s00262-022-03282-6
Bao, S. et al. TGF-β1 induces immune escape by enhancing PD-1 and CTLA-4 expression on T lymphocytes in hepatocellular carcinoma. Front. Oncol. 11, 694145 (2021).
pubmed: 34249750
pmcid: 8270637
doi: 10.3389/fonc.2021.694145
Hernández-Vega, A. M. & Camacho-Arroyo, I. Crosstalk between 17β-estradiol and TGF-β signaling modulates glioblastoma progression. Brain Sci. 11(5), 564 (2021).
pubmed: 33925221
pmcid: 8145480
doi: 10.3390/brainsci11050564
Ito, I. et al. Estrogen inhibits transforming growth factor beta signaling by promoting Smad2/3 degradation. J. Biol. Chem. 285(19), 14747–14755 (2010).
pubmed: 20207742
pmcid: 2863224
doi: 10.1074/jbc.M109.093039
Vazquez Rodriguez, G. et al. Estradiol promotes breast cancer cell migration via recruitment and activation of neutrophils. Cancer Immunol. Res. 5(3), 234–247 (2017).
pubmed: 28159748
doi: 10.1158/2326-6066.CIR-16-0150
Ghafouri-Fard, S. et al. The impact of the phytotherapeutic agent quercetin on expression of genes and activity of signaling pathways. Biomed. Pharmacother. 141, 111847 (2021).
pubmed: 34198048
doi: 10.1016/j.biopha.2021.111847
Alnusaire, T. S. et al. Revealing the underlying mechanism of acacia nilotica against asthma from a systematic perspective: A network pharmacology and molecular docking study. Life (Basel) 13(2), 411 (2023).
pubmed: 36836768
Jiao, P. et al. Integrating network pharmacology and experimental validation to elucidate the mechanism of Yiqi Yangyin decoction in suppressing non-small-cell lung cancer. Biomed. Res. Int. 2023, 4967544 (2023).
pubmed: 36874921
pmcid: 9980286
doi: 10.1155/2023/4967544
Khalid, H. R. et al. Integrated system pharmacology approaches to elucidate multi-target mechanism of solanum surattense against hepatocellular carcinoma. Molecules 27(19), 6220 (2022).
pubmed: 36234758
pmcid: 9570789
doi: 10.3390/molecules27196220
Liu, M. et al. Investigation of the underlying mechanism of Huangqi-Dangshen for myasthenia gravis treatment via molecular docking and network pharmacology. Evid. Based Complement Alternat. Med. 2023, 5301024 (2023).
pubmed: 36818231
pmcid: 9935813
doi: 10.1155/2023/5301024
Pan, J. et al. Qingfei Jiedu decoction inhibits PD-L1 expression in lung adenocarcinoma based on network pharmacology analysis, molecular docking and experimental verification. Front. Pharmacol. 13, 897966 (2022).
pubmed: 36091822
pmcid: 9454399
doi: 10.3389/fphar.2022.897966
Chen, X. et al. EGFR and ERK activation resists flavonoid quercetin-induced anticancer activities in human cervical cancer cells in vitro. Oncol. Lett. 22(5), 754 (2021).
pubmed: 34539858
pmcid: 8436358
doi: 10.3892/ol.2021.13015
Yu, F., Jiang, L. L. & Di, Y. C. Effect of quercetin on heat shock protein 27 expression in prostate cancer cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 36(5), 506–509 (2014).
pubmed: 25360648
Parcellier, A. et al. HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation. Mol. Cell Biol. 23(16), 5790–5802 (2003).
pubmed: 12897149
pmcid: 166315
doi: 10.1128/MCB.23.16.5790-5802.2003
Pozios, I. et al. Raloxifene inhibits pancreatic adenocarcinoma growth by interfering with ERβ and IL-6/gp130/STAT3 signaling. Cell. Oncol. (Dordr) 44(1), 167–177 (2021).
pubmed: 32940862
doi: 10.1007/s13402-020-00559-9
Luo, P. et al. Raloxifene inhibits IL-6/STAT3 signaling pathway and protects against high-fat-induced atherosclerosis in ApoE(-/-) mice. Life Sci. 261, 118304 (2020).
pubmed: 32828944
doi: 10.1016/j.lfs.2020.118304
Kim, L. et al. Bazedoxifene, a GP130 inhibitor, modulates emt signaling and exhibits antitumor effects in HPV-positive cervical cancer. Int. J. Mol. Sci. 22(16), 8693 (2021).
pubmed: 34445405
pmcid: 8395523
doi: 10.3390/ijms22168693
Tian, J. et al. Bazedoxifene is a novel IL-6/GP130 inhibitor for treating triple-negative breast cancer. Breast Cancer Res. Treat. 175(3), 553–566 (2019).
pubmed: 30852762
doi: 10.1007/s10549-019-05183-2
Song, W. et al. Bazedoxifene plays a protective role against inflammatory injury of endothelial cells by targeting CD40. Cardiovasc. Ther. 2020, 1795853 (2020).
pubmed: 33381228
pmcid: 7755478
doi: 10.1155/2020/1795853
Fahmy, U. A. et al. Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells. Drug Deliv. 29(1), 1863–1877 (2022).
pubmed: 35708464
pmcid: 9225738
doi: 10.1080/10717544.2022.2072544
Ma, Y. et al. Raloxifene, identified as a novel LSD1 inhibitor, suppresses the migration of renal cell carcinoma. Future Med. Chem. 13(6), 533–542 (2021).
pubmed: 33527838
doi: 10.4155/fmc-2020-0323
Chen, S. et al. In vitro and in silico analyses of the inhibition of human aldehyde oxidase by bazedoxifene, lasofoxifene, and structural analogues. J. Pharmacol. Exp. Ther. 371(1), 75–86 (2019).
pubmed: 31289113
doi: 10.1124/jpet.119.259267
Beedham, C. Aldehyde oxidase; new approaches to old problems. Xenobiotica 50(1), 34–50 (2020).
pubmed: 31149862
doi: 10.1080/00498254.2019.1626029
Manevski, N. et al. Metabolism by aldehyde oxidase: Drug design and complementary approaches to challenges in drug discovery. J. Med. Chem. 62(24), 10955–10994 (2019).
pubmed: 31385704
doi: 10.1021/acs.jmedchem.9b00875
Pettersen, E. F. et al. UCSF Chimera—A visualization system for exploratory research and analysis. J. Comput. Chem. 25(13), 1605–1612 (2004).
pubmed: 15264254
doi: 10.1002/jcc.20084
Biovia, D.S., BIOVIA Discovery Studio Visualizer (2D diagram and scheme of the interactions with amino acids). 2020, BIOVIA Workbook: San Diego, USA.
Backman, T. W., Cao, Y. & Girke, T. ChemMine tools: An online service for analyzing and clustering small molecules. Nucleic Acids Res. 39, W486-91 (2011).
pubmed: 21576229
pmcid: 3125754
doi: 10.1093/nar/gkr320
Krieger, E. et al. Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8. Proteins 77(Suppl 9), 114–22 (2009).
pubmed: 19768677
pmcid: 2922016
doi: 10.1002/prot.22570
Vangone, A. et al. Large-scale prediction of binding affinity in protein-small ligand complexes: The PRODIGY-LIG web server. Bioinformatics 35(9), 1585–1587 (2019).
pubmed: 31051038
doi: 10.1093/bioinformatics/bty816