Araştırma Makalesi
BibTex RIS Kaynak Göster
Yıl 2024, Cilt: 10 Sayı: 3, 109 - 117, 28.10.2024
https://doi.org/10.30934/kusbed.1530079

Öz

Kaynakça

  • Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
  • Falzone L, Salomone S, Libra M. Evolution of cancer pharmacological treatments at the turn of the third millennium. Front Pharmacol. 2018;9:1300.
  • Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651-668.
  • Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019;18(3):175-196.
  • Kruger S, Ilmer M, Kobold S, et al. Advances in cancer immunotherapy 2019–latest trends. J Exp Clin Cancer Res. 2019;38(1):1-11.
  • Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355.
  • Tokunaga R, Zhang W, Naseem M, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation–a target for novel cancer therapy. Cancer Treat Rev. 2018;63:40-47.
  • Fulton AM. The chemokine receptors CXCR4 and CXCR3 in cancer. Curr Oncol Rep. 2009;11:125-131.
  • O'Hayre M, Salanga CL, Handel TM, Allen SJ. Chemokines and cancer: migration, intracellular signalling and intercellular communication in the microenvironment. Biochem J. 2008;409(3):635-649.
  • Ehlert JE, Addison CA, Burdick MD, Kunkel SL, Strieter RM. Identification and partial characterization of a variant of human CXCR3 generated by posttranscriptional exon skipping. J Immunol. 2004;173(10):6234-6240.
  • Mikucki ME, Fisher DT, Matsuzaki J, et al. Non-redundant requirement for CXCR3 signaling during tumoricidal T-cell trafficking across tumor vascular checkpoints. Nat Commun. 2015;6(1):1-14.
  • Balestrieri ML, Balestrieri A, Mancini FP, Napoli C. Understanding the immunoangiostatic CXC chemokine network. Cardiovasc Res. 2008;78(2):250-256.
  • Romagnani P, Maggi L, Mazzinghi B, et al. CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production. J Allergy Clin Immunol. 2005;116(6):1372-1379.
  • Barbieri F, Bajetto A, Florio T. Role of chemokine network in the development and progression of ovarian cancer: a potential novel pharmacological target. J Oncol. 2010;2010:426956.
  • Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007;7(2):79-94.
  • Cambien B, Karimdjee BF, Richard-Fiardo P, et al. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009;100(11):1755-1764.
  • Ma X, Norsworthy K, Kundu N, et al. CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model. Mol Cancer Ther. 2009;8(3):490-498.
  • Klatte T, Seligson DB, Leppert JT, et al. The chemokine receptor CXCR3 is an independent prognostic factor in patients with localized clear cell renal cell carcinoma. J Urol. 2008;179(1):61-66.
  • Kondo T, Ito F, Nakazawa H, Horita S, Osaka Y, Toma H. High expression of chemokine gene as a favorable prognostic factor in renal cell carcinoma. J Urol. 2004;171(6):2171-2175.
  • Li K, Zhu Z, Luo J, et al. Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer. Int J Clin Exp Pathol. 2015;8(11):14725.
  • Chen F, Yin S, Niu L, et al. Expression of the chemokine receptor CXCR3 correlates with dendritic cell recruitment and prognosis in gastric cancer. Genet Test Mol Biomarkers. 2018;22(1):35-42.
  • Monteagudo C, Martin JM, Jorda E, Llombart-Bosch A. CXCR3 chemokine receptor immunoreactivity in primary cutaneous malignant melanoma: correlation with clinicopathological prognostic factors. J Clin Pathol. 2007;60(6):596-599.
  • Oghumu S, Varikuti S, Terrazas C, et al. CXCR3 deficiency enhances tumor progression by promoting macrophage M2 polarization in a murine breast cancer model. Immunology. 2014;143(1):109-119.
  • Li L, Chen J, Lu ZH, et al. Significance of chemokine receptor CXCR3 expression in breast cancer. Zhonghua Bing Li Xue Za Zhi. 2011;40(2):85-88.
  • Sharma I, Siraj F, Sharma KC, Singh A. Immunohistochemical expression of chemokine receptor CXCR3 and its ligand CXCL10 in low-grade astrocytomas and glioblastoma multiforme: A tissue microarray-based comparison. J Cancer Res Ther. 2016;12(2):793-797.
  • Jin Q, Ding J, Liu Y, Chen C, Wang S. CXCR3 blockade inhibits glioma cell migration, invasion and angiogenesis. Oncol Lett. 2021;21(5):1-7.
  • Peng D, Kryczek I, Nagarsheth N, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature. 2015;527(7577):249-253.
  • Walser TC, Rifat S, Ma X, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006;66(15):7701-7707.
  • Tonn GR, Wong SG, Wong SC, et al. An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. J Autoimmun. 2009;32(2):77-84.
  • Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016;5:e47.
  • Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal. 2013;2013:162750.
  • Pérez-Cano FJ, Castell M. Flavonoids, inflammation and immune system. Nutrients. 2016;8(10):659.
  • Terao J. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function. Biochem Pharmacol. 2017;139:15-23.
  • Ravishankar D, Rajora AK, Greco F, Osborn HM. Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol. 2013;45(12):2821-2831.
  • Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev. 2011;5(9):1-12.
  • Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech. 2013;3(6):439-459.
  • Abotaleb M, Samuel SM, Varghese E, et al. Flavonoids in cancer and apoptosis. Cancers (Basel). 2018;11(1):28.
  • Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020;12(2):457.
  • Li W, Li X, Wang W, et al. Quercetin inhibits the proliferation of glycolysis-addicted HCC cells by reducing hexokinase 2 and Akt-mTOR pathway. Molecules. 2019;24(10):1993.
  • Budhraja A, Gao N, Zhang Z, et al. Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. Mol Cancer Ther. 2012;11(1):132-142.
  • Frisch, M. J. E. A., Trucks, G. W., Schlegel, H. B., et al. (2009). Gaussian 09, Gaussian. Inc., Wallingford CT, 121, 150-166.
  • Trott, O., Olson, A. J. (2010). 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.
  • Demirag AD, Çelik S, Arslan S, Özel A, Akyüz S. The inhibitory activity of Ruxolitinib against COVID-19 major protease enzyme and SARS CoV-2 spike glycoprotein: A molecular docking study. Open J Nano. 2023;8(2):65-73.
  • Release, S. (2017). 1: Maestro. Schrödinger, LLC, New York, NY, 2017.
  • Wijtmans M, Verzijl D, Bergmans S, et al. CXCR3 antagonists: quaternary ammonium salts equipped with biphenyl-and polycycloaliphatic-anchors. Bioorg Med Chem. 2011;19(11):3384-3393.
  • McGuinness BF, Carroll CD, Zawacki LG, et al. Novel CXCR3 antagonists with a piperazinyl-piperidine core. Bioorg Med Chem Lett. 2009;19(17):5205-5208.
  • Liu JP, Zhang M, Wang WY, Grimsgaard S. Chinese herbal medicines for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;(3):CD003642.
  • Zhang Y, Garcia-Ibanez L, Toellner KM. Regulation of germinal center B-cell differentiation. Immunol Rev. 2016;270(1):8-19.
  • Jenh CH, Cox MA, Cui L, et al. A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmune diseases and delays graft rejection. BMC Immunol. 2012;13:2.

CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy

Yıl 2024, Cilt: 10 Sayı: 3, 109 - 117, 28.10.2024
https://doi.org/10.30934/kusbed.1530079

Öz

Objective: To investigate the interactions between select flavonoids (Luteolin, Quercetin, Apigenin, Kaempferol, and Amorphine) and the CXCR3 receptor, evaluating their potential as novel therapeutic agents in cancer immunotherapy.

Methods: Molecular docking simulations were employed to analyze flavonoid-CXCR3 receptor interactions. Comprehensive in silico ADMET analyses were conducted to assess pharmacokinetic properties and toxicity profiles of the compounds.

Results: Flavonoids exhibited high-affinity binding to the CXCR3 receptor, with binding affinities ranging from -8.7 to -13.0 kcal/mol. Amorphine demonstrated the highest binding affinity (-13.0 kcal/mol), indicating superior inhibition potential. Luteolin showed optimal ADME characteristics, including favorable oral bioavailability (62%) and blood-brain barrier permeability (log BB -1.911). Molecular docking analyses identified critical amino acid residues (TYR205, TYR308, TRP109, PHE131, and ASN132) in flavonoid-CXCR3 interactions. In silico toxicity predictions suggested low risk profiles for all examined flavonoids.

Conclusion: This study provides evidence for the potential of flavonoids as CXCR3 receptor antagonists in cancer immunotherapy. The elucidated molecular interactions and favorable ADMET profiles warrant further investigation of these compounds. Future research should focus on optimization of flavonoid-based CXCR3 inhibitors, preclinical and clinical evaluations, and assessment of their immunomodulatory effects within the tumor microenvironment. These findings contribute to the development of novel, flavonoid-derived therapeutic strategies in cancer treatment.

Kaynakça

  • Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
  • Falzone L, Salomone S, Libra M. Evolution of cancer pharmacological treatments at the turn of the third millennium. Front Pharmacol. 2018;9:1300.
  • Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651-668.
  • Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019;18(3):175-196.
  • Kruger S, Ilmer M, Kobold S, et al. Advances in cancer immunotherapy 2019–latest trends. J Exp Clin Cancer Res. 2019;38(1):1-11.
  • Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355.
  • Tokunaga R, Zhang W, Naseem M, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation–a target for novel cancer therapy. Cancer Treat Rev. 2018;63:40-47.
  • Fulton AM. The chemokine receptors CXCR4 and CXCR3 in cancer. Curr Oncol Rep. 2009;11:125-131.
  • O'Hayre M, Salanga CL, Handel TM, Allen SJ. Chemokines and cancer: migration, intracellular signalling and intercellular communication in the microenvironment. Biochem J. 2008;409(3):635-649.
  • Ehlert JE, Addison CA, Burdick MD, Kunkel SL, Strieter RM. Identification and partial characterization of a variant of human CXCR3 generated by posttranscriptional exon skipping. J Immunol. 2004;173(10):6234-6240.
  • Mikucki ME, Fisher DT, Matsuzaki J, et al. Non-redundant requirement for CXCR3 signaling during tumoricidal T-cell trafficking across tumor vascular checkpoints. Nat Commun. 2015;6(1):1-14.
  • Balestrieri ML, Balestrieri A, Mancini FP, Napoli C. Understanding the immunoangiostatic CXC chemokine network. Cardiovasc Res. 2008;78(2):250-256.
  • Romagnani P, Maggi L, Mazzinghi B, et al. CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production. J Allergy Clin Immunol. 2005;116(6):1372-1379.
  • Barbieri F, Bajetto A, Florio T. Role of chemokine network in the development and progression of ovarian cancer: a potential novel pharmacological target. J Oncol. 2010;2010:426956.
  • Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007;7(2):79-94.
  • Cambien B, Karimdjee BF, Richard-Fiardo P, et al. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009;100(11):1755-1764.
  • Ma X, Norsworthy K, Kundu N, et al. CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model. Mol Cancer Ther. 2009;8(3):490-498.
  • Klatte T, Seligson DB, Leppert JT, et al. The chemokine receptor CXCR3 is an independent prognostic factor in patients with localized clear cell renal cell carcinoma. J Urol. 2008;179(1):61-66.
  • Kondo T, Ito F, Nakazawa H, Horita S, Osaka Y, Toma H. High expression of chemokine gene as a favorable prognostic factor in renal cell carcinoma. J Urol. 2004;171(6):2171-2175.
  • Li K, Zhu Z, Luo J, et al. Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer. Int J Clin Exp Pathol. 2015;8(11):14725.
  • Chen F, Yin S, Niu L, et al. Expression of the chemokine receptor CXCR3 correlates with dendritic cell recruitment and prognosis in gastric cancer. Genet Test Mol Biomarkers. 2018;22(1):35-42.
  • Monteagudo C, Martin JM, Jorda E, Llombart-Bosch A. CXCR3 chemokine receptor immunoreactivity in primary cutaneous malignant melanoma: correlation with clinicopathological prognostic factors. J Clin Pathol. 2007;60(6):596-599.
  • Oghumu S, Varikuti S, Terrazas C, et al. CXCR3 deficiency enhances tumor progression by promoting macrophage M2 polarization in a murine breast cancer model. Immunology. 2014;143(1):109-119.
  • Li L, Chen J, Lu ZH, et al. Significance of chemokine receptor CXCR3 expression in breast cancer. Zhonghua Bing Li Xue Za Zhi. 2011;40(2):85-88.
  • Sharma I, Siraj F, Sharma KC, Singh A. Immunohistochemical expression of chemokine receptor CXCR3 and its ligand CXCL10 in low-grade astrocytomas and glioblastoma multiforme: A tissue microarray-based comparison. J Cancer Res Ther. 2016;12(2):793-797.
  • Jin Q, Ding J, Liu Y, Chen C, Wang S. CXCR3 blockade inhibits glioma cell migration, invasion and angiogenesis. Oncol Lett. 2021;21(5):1-7.
  • Peng D, Kryczek I, Nagarsheth N, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature. 2015;527(7577):249-253.
  • Walser TC, Rifat S, Ma X, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006;66(15):7701-7707.
  • Tonn GR, Wong SG, Wong SC, et al. An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. J Autoimmun. 2009;32(2):77-84.
  • Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016;5:e47.
  • Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal. 2013;2013:162750.
  • Pérez-Cano FJ, Castell M. Flavonoids, inflammation and immune system. Nutrients. 2016;8(10):659.
  • Terao J. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function. Biochem Pharmacol. 2017;139:15-23.
  • Ravishankar D, Rajora AK, Greco F, Osborn HM. Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol. 2013;45(12):2821-2831.
  • Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev. 2011;5(9):1-12.
  • Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech. 2013;3(6):439-459.
  • Abotaleb M, Samuel SM, Varghese E, et al. Flavonoids in cancer and apoptosis. Cancers (Basel). 2018;11(1):28.
  • Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020;12(2):457.
  • Li W, Li X, Wang W, et al. Quercetin inhibits the proliferation of glycolysis-addicted HCC cells by reducing hexokinase 2 and Akt-mTOR pathway. Molecules. 2019;24(10):1993.
  • Budhraja A, Gao N, Zhang Z, et al. Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. Mol Cancer Ther. 2012;11(1):132-142.
  • Frisch, M. J. E. A., Trucks, G. W., Schlegel, H. B., et al. (2009). Gaussian 09, Gaussian. Inc., Wallingford CT, 121, 150-166.
  • Trott, O., Olson, A. J. (2010). 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.
  • Demirag AD, Çelik S, Arslan S, Özel A, Akyüz S. The inhibitory activity of Ruxolitinib against COVID-19 major protease enzyme and SARS CoV-2 spike glycoprotein: A molecular docking study. Open J Nano. 2023;8(2):65-73.
  • Release, S. (2017). 1: Maestro. Schrödinger, LLC, New York, NY, 2017.
  • Wijtmans M, Verzijl D, Bergmans S, et al. CXCR3 antagonists: quaternary ammonium salts equipped with biphenyl-and polycycloaliphatic-anchors. Bioorg Med Chem. 2011;19(11):3384-3393.
  • McGuinness BF, Carroll CD, Zawacki LG, et al. Novel CXCR3 antagonists with a piperazinyl-piperidine core. Bioorg Med Chem Lett. 2009;19(17):5205-5208.
  • Liu JP, Zhang M, Wang WY, Grimsgaard S. Chinese herbal medicines for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;(3):CD003642.
  • Zhang Y, Garcia-Ibanez L, Toellner KM. Regulation of germinal center B-cell differentiation. Immunol Rev. 2016;270(1):8-19.
  • Jenh CH, Cox MA, Cui L, et al. A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmune diseases and delays graft rejection. BMC Immunol. 2012;13:2.
Toplam 50 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Biyoinformatik ve Hesaplamalı Biyoloji (Diğer), İç Hastalıkları
Bölüm Özgün Araştırma / Tıp Bilimleri
Yazarlar

Hatice Güngör 0000-0001-6142-2432

A. Demet Demirag 0000-0002-9609-9150

Yayımlanma Tarihi 28 Ekim 2024
Gönderilme Tarihi 8 Ağustos 2024
Kabul Tarihi 12 Eylül 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 10 Sayı: 3

Kaynak Göster

APA Güngör, H., & Demirag, A. D. (2024). CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, 10(3), 109-117. https://doi.org/10.30934/kusbed.1530079
AMA Güngör H, Demirag AD. CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy. KOU Sag Bil Derg. Ekim 2024;10(3):109-117. doi:10.30934/kusbed.1530079
Chicago Güngör, Hatice, ve A. Demet Demirag. “CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 10, sy. 3 (Ekim 2024): 109-17. https://doi.org/10.30934/kusbed.1530079.
EndNote Güngör H, Demirag AD (01 Ekim 2024) CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 10 3 109–117.
IEEE H. Güngör ve A. D. Demirag, “CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy”, KOU Sag Bil Derg, c. 10, sy. 3, ss. 109–117, 2024, doi: 10.30934/kusbed.1530079.
ISNAD Güngör, Hatice - Demirag, A. Demet. “CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 10/3 (Ekim 2024), 109-117. https://doi.org/10.30934/kusbed.1530079.
JAMA Güngör H, Demirag AD. CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy. KOU Sag Bil Derg. 2024;10:109–117.
MLA Güngör, Hatice ve A. Demet Demirag. “CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, c. 10, sy. 3, 2024, ss. 109-17, doi:10.30934/kusbed.1530079.
Vancouver Güngör H, Demirag AD. CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy. KOU Sag Bil Derg. 2024;10(3):109-17.