Exploring the Therapeutic Potential of Fluorinated CXCR4 Inhibitor A1: Insights from Breast Cancer In Vitro Investigations
-
Ali Rahimi
,
Hossein Khorramdelazad
,
Ali Darehkordi
,
Gholamhossein Hassanshahi
,
Majid Khoshmirsafa
,
Milad Karimi
,
Reza Falak
,
Elaheh Safari
Abstract
The impacts of the CXC motif chemokine 12 (CXCL12)/ C-X-C chemokine receptor type 4 (CXCR4) axis on the infiltration of anti-tumor and pro-tumor immune cells in the tumor microenvironment (TME) of breast cancer (BCa) have been noted in previous studies. Accordingly, regulating the downstream signals of this axis can effectively increase CD8+ cytotoxic T cells and decrease the frequency of immunosuppressive cells in the TME. This study investigated the anti-tumor effects of N, N''-thiocarbonylbis (N'-(3,4-dimethylphenyl)-2,2,2 trifluoroacetimidamide) (A1), a novel fluorinated CXCR4 inhibitor on a BCa cell line.
In this study, the impacts of A1 on cell viability, proliferation, apoptosis, and cell cycle were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. Moreover, the effect of A1 on the number of CXCR4+ 4T1 cells was measured by flow cytometry.
A1 treatment exhibited cytotoxic effects on 4T1 cells, promoting cell apoptosis and G2/M cell cycle arrest. In addition, A1-treated cells showed a reduced cell proliferation than CXCL12 treated cells. Furthermore, treatment with A1 alongside CXCL12 significantly decreased the number of CXCR4+ cells compared to the control group treated with only CXCL12 as a proliferator factor.
These results indicate that A1 exerts potential anti-tumor effects and may serve as a possible therapeutic agent for BCa treatment; however, further studies are required.
1. Polyak K. On the birth of breast cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2001;1552(1):1-13.
2. Goh CY, Wyse C, Ho M, O'Beirne E, Howard J, Lindsay S, et al. Exosomes in triple negative breast cancer: Garbage disposals or Trojan horses? Cancer lett. 2020;473:90-7.
3. Ang L, Guo L, Wang J, Huang J, Lou X, Zhao M. Oncolytic virotherapy armed with an engineered interfering lncRNA exhibits antitumor activity by blocking the epithelial mesenchymal transition in triple-negative breast cancer. Cancer Lett. 2020;479:42-53.
4. Ogony JW, Radisky DC, Ruddy KJ, Goodison S, Wickland DP, Egan KM, et al. Immune responses and risk of triple-negative breast cancer: implications for higher rates among African American women. Cancer Prevent Res. 2020;13(11):901-10.
5. Standish LJ, Sweet ES, Novack J, Wenner CA, Bridge C, Nelson A, et al. Breast cancer and the immune system. J Society Integrative Oncol. 2008;6(4):158.
6. Arang N, Gutkind JS. G Protein‐Coupled receptors and heterotrimeric G proteins as cancer drivers. FEBS lett. 2020;594(24):4201-32.
7. Mollica Poeta V, Massara M, Capucetti A, Bonecchi R. Chemokines and chemokine receptors: new targets for cancer immunotherapy. Front Immunol. 2019;10:379.
8. Newman LA, Jenkins B, Chen Y, Oppong JK, Adjei E, Jibril AS, et al. Hereditary susceptibility for triple negative breast cancer associated with western sub-saharan african ancestry: Results from an international surgical breast cancer collaborative. Ann Surgery. 2019;270(3):484-92.
9. Lai WY, Mueller A. Latest update on chemokine receptors as therapeutic targets. Biochem Society Trans. 2021;49(3):1385-95.
10. Zhou W, Guo S, Liu M, Burow ME, Wang G. Targeting CXCL12/CXCR4 axis in tumor immunotherapy. Curr Med Chemistry. 2019;26(17):3026-41.
11. Shi Y, Riese DJ, Shen J. The role of the CXCL12/CXCR4/CXCR7 chemokine axis in cancer. Front Pharmacol. 2020;11:574667.
12. Wu V, Yeerna H, Nohata N, Chiou J, Harismendy O, Raimondi F, et al. Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy. J Biol Chemistry. 2019;294(29):11062-86.
13. Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res. 2010;16(11):2927-31.
14. Liang S, Peng X, Li X, Yang P, Xie L, Li Y, et al. Silencing of CXCR4 sensitizes triple-negative breast cancer cells to cisplatin. Oncotarget. 2015;6(2):1020.
15. Yang P, Liang S-X, Huang W-H, Zhang H-W, Li X-L, Xie L-H, et al. Aberrant expression of CXCR4 significantly contributes to metastasis and predicts poor clinical outcome in breast cancer. Curr Mol Med. 2014;14(1):174-84.
16. Zhao S, Wu B, Stevens RC. Advancing chemokine GPCR structure based drug discovery. Structure. 2019;27(3):405-8.
17. Zhou K, Xie L, Peng X, Guo Q, Wu Q, Wang W, et al. CXCR4 antagonist AMD3100 enhances the response of MDA-MB-231 triple-negative breast cancer cells to ionizing radiation. Cancer lett. 2018;418:196-203.
18. Hinton CV, Avraham S, Avraham HK. Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain. Clin Exp Metastasis. 2010;27:97-105.
19. Khalid M, Hussain MT, Hanif M, Qadeer G, Rama NH, Kornienko A, Khan KM. Synthesis and anti-cancer, anti-metastatic evaluation of some new fluorinated isocoumarins and 3, 4-dihydroisocoumarins. J Fluorine Chemistry. 2012;135:240-5.
20. Khorramdelazad H, Bagherzadeh K, Rahimi A, Safari E, Hassanshahi G, Khoshmirsafa M, et al. Antitumor activities of a novel fluorinated small molecule (A1) in CT26 colorectal cancer cells: molecular docking and in vitro studies. J Biomol Structure Dynamics. 2023:1-14.
21. He Y, Zhu Q, Chen M, Huang Q, Wang W, Li Q, et al. The changing 50% inhibitory concentration (IC50) of cisplatin: a pilot study on the artifacts of the MTT assay and the precise measurement of density-dependent chemoresistance in ovarian cancer. Oncotarget. 2016;7(43):70803.
22. Ke B, Tian M, Li J, Liu B, He G. Targeting programmed cell death using small‐molecule compounds to improve potential cancer therapy. Med Res Rev. 2016;36(6):983-1035.
23. Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N, Slamon DJ. Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro. Breast cancer Res Treat. 2007;105:319-26.
24. Zielińska KA, Katanaev VL. The signaling duo CXCL12 and CXCR4: Chemokine fuel for breast cancer tumorigenesis. Cancers. 2020;12(10):3071.
25. Liu T, Li X, You S, Bhuyan SS, Dong L. Effectiveness of AMD3100 in treatment of leukemia and solid tumors: from original discovery to use in current clinical practice. Exp Hematol Oncol. 2015;5:1-11.
26. Jung H, Paust S. Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy. Front Immunol. 2024;15:1443366.
27. Martins JRdS. The role of CXCR4 in cancer exosomes and metastasis 2018.
28. Mousavi A. CXCL12/CXCR4 signal transduction in diseases and its molecular approaches in targeted-therapy. Immunol Lett. 2020;217:91-115.
29. Chinni SR, Sivalogan S, Dong Z, Filho JCT, Deng X, Bonfil RD, Cher ML. CXCL12/CXCR4 signaling activates Akt‐1 and MMP‐9 expression in prostate cancer cells: the role of bone microenvironment‐associated CXCL12. Prostate. 2006;66(1):32-48.
30. Li YM, Pan Y, Wei Y, Cheng X, Zhou BP, Tan M, et al. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. Cancer cell. 2004;6(5):459-69.
31. Kittang AO, Kordasti S, Sand KE, Costantini B, Kramer AM, Perezabellan P, et al. Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome. Oncoimmunology. 2016;5(2):e1062208.
32. D'agostino G, Saporito A, Cecchinato V, Silvestri Y, Borgeat A, Anselmi L, Uguccioni M. Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration. British J Anaesthesia. 2018;121(4):962-8.
33. Lefort S, Thuleau A, Kieffer Y, Sirven P, Bieche I, Marangoni E, et al. CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancer patients. Oncogene. 2017;36(9):1211-22.
34. Xu C, Zhao H, Chen H, Yao Q. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther. 2015:4953-64.
35. Tamamura H, Hori A, Kanzaki N, Hiramatsu K, Mizumoto M, Nakashima H, et al. T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer. FEBS lett. 2003;550(1-3):79-83.
36. Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007;7(2):79-94.
37. Cavnar S, Ray P, Moudgil P, Chang S, Luker K, Linderman J, et al. Microfluidic source-sink model reveals effects of biophysically distinct CXCL12 isoforms in breast cancer chemotaxis. Integrative Biol. 2014;6(5):564-76.
38. Hirbe AC, Rubin J, Uluçkan Ö, Morgan EA, Eagleton MC, Prior JL, et al. Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone. Proc Natl Acad Sci U S A. 2007;104(35):14062-7.
39. Larochelle A, Krouse A, Metzger M, Orlic D, Donahue RE, Fricker S, et al. AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates. Blood. 2006;107(9):3772-8.
40. Luo Z, Wang B, Chen Y, Liu H, Shi L. Novel CXCR4 Inhibitor CPZ1344 Inhibits the Proliferation, Migration and Angiogenesis of Glioblastoma. Pathol Oncol Res. 2020;26:2597-604.
41. Leelawat K, Keeratichamroen S, Leelawat S, Tohtong R. CD24 induces the invasion of cholangiocarcinoma cells by upregulating CXCR4 and increasing the phosphorylation of ERK1/2. Oncol lett. 2013;6(5):1439-46.
42. Mayr C, Neureiter D, Pichler M, Berr F, Wagner A, Kiesslich T, Namberger K. Cytotoxic effects of chemokine receptor 4 inhibition by AMD3100 in biliary tract cancer cells: Potential drug synergism with gemcitabine. Mol Med Rep. 2015;12(2):2247-52.
43. Berghuis D, Schilham MW, Santos SJ, Savola S, Knowles HJ, Dirksen U, et al. The CXCR4-CXCL12 axis in Ewing sarcoma: promotion of tumor growth rather than metastatic disease. Clin Sarcoma Res. 2012;2:1-9.
44. Liao Y-X, Fu Z-Z, Zhou C-H, Shan L-C, Wang ZY, Yin F, et al. AMD3100 reduces CXCR4-mediated survival and metastasis of osteosarcoma by inhibiting JNK and Akt, but not p38 or Erk1/2, pathways in in vitro and mouse experiments. Oncol Rep. 2015;34(1):33-42.
45. Qiu J, Zhao B, Shen Y, Chen W, Ma Y, Shen Y. A novel p-terphenyl derivative inducing cell-cycle arrest and apoptosis in MDA-MB-435 cells through topoisomerase inhibition. Europ J Med Chemistry. 2013;68:192-202.
46. Goodell JR, Ougolkov AV, Hiasa H, Kaur H, Remmel R, Billadeau DD, Ferguson DM. Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis. J Med Chemistry. 2008;51(2):179-82.
47. Morein D, Erlichman N, Ben-Baruch A. Beyond cell motility: the expanding roles of chemokines and their receptors in malignancy. Front Immunol. 2020;11:952.
48. McConnell AT. Implications of MEK and VEGFR2 inhibition on melanoma CXCR4-CXCL12 chemotaxis, survival and tumour progression: Newcastle University; 2017.
49. Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863(12):2977-92.
50. Esmaeili MA, Farimani MM, Kiaei M. Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS-mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2) cells. Mol Cell Biochemistry. 2014;397:17-31.
51. Löbrich M, Jeggo PA. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Na Rev Cancer. 2007;7(11):861-9.
52. Wang F-Z, Fei H-r, Cui Y-J, Sun Y-K, Li Z-M, Wang X-Y, et al. The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Apoptosis. 2014;19:1389-98.
53. Balkwill F, editor The significance of cancer cell expression of the chemokine receptor CXCR4. Seminars Cancer Biol; 2004: Elsevier.
54. Darash-Yahana M, Pikarsky E, Abramovitch R, Zeira E, Pal B, Karplus R, et al. Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. FASEB J. 2004;18(11):1240-2.
55. Ishikawa T, Nakashiro K-I, Klosek SK, Goda H, Hara S, Uchida D, Hamakawa H. Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma. Oncol Reports. 2009;21(3):707-12.
56. Spinello I, Quaranta M, Riccioni R, Riti V, Pasquini L, Boe A, et al. MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias. Blood Cancer J. 2011;1(6):e26-e.
57. Neel NF, Schutyser E, Sai J, Fan G-H, Richmond A. Chemokine receptor internalization and intracellular trafficking. Cytokine Growth Factor Rev. 2005;16(6):637-58.
2. Goh CY, Wyse C, Ho M, O'Beirne E, Howard J, Lindsay S, et al. Exosomes in triple negative breast cancer: Garbage disposals or Trojan horses? Cancer lett. 2020;473:90-7.
3. Ang L, Guo L, Wang J, Huang J, Lou X, Zhao M. Oncolytic virotherapy armed with an engineered interfering lncRNA exhibits antitumor activity by blocking the epithelial mesenchymal transition in triple-negative breast cancer. Cancer Lett. 2020;479:42-53.
4. Ogony JW, Radisky DC, Ruddy KJ, Goodison S, Wickland DP, Egan KM, et al. Immune responses and risk of triple-negative breast cancer: implications for higher rates among African American women. Cancer Prevent Res. 2020;13(11):901-10.
5. Standish LJ, Sweet ES, Novack J, Wenner CA, Bridge C, Nelson A, et al. Breast cancer and the immune system. J Society Integrative Oncol. 2008;6(4):158.
6. Arang N, Gutkind JS. G Protein‐Coupled receptors and heterotrimeric G proteins as cancer drivers. FEBS lett. 2020;594(24):4201-32.
7. Mollica Poeta V, Massara M, Capucetti A, Bonecchi R. Chemokines and chemokine receptors: new targets for cancer immunotherapy. Front Immunol. 2019;10:379.
8. Newman LA, Jenkins B, Chen Y, Oppong JK, Adjei E, Jibril AS, et al. Hereditary susceptibility for triple negative breast cancer associated with western sub-saharan african ancestry: Results from an international surgical breast cancer collaborative. Ann Surgery. 2019;270(3):484-92.
9. Lai WY, Mueller A. Latest update on chemokine receptors as therapeutic targets. Biochem Society Trans. 2021;49(3):1385-95.
10. Zhou W, Guo S, Liu M, Burow ME, Wang G. Targeting CXCL12/CXCR4 axis in tumor immunotherapy. Curr Med Chemistry. 2019;26(17):3026-41.
11. Shi Y, Riese DJ, Shen J. The role of the CXCL12/CXCR4/CXCR7 chemokine axis in cancer. Front Pharmacol. 2020;11:574667.
12. Wu V, Yeerna H, Nohata N, Chiou J, Harismendy O, Raimondi F, et al. Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy. J Biol Chemistry. 2019;294(29):11062-86.
13. Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res. 2010;16(11):2927-31.
14. Liang S, Peng X, Li X, Yang P, Xie L, Li Y, et al. Silencing of CXCR4 sensitizes triple-negative breast cancer cells to cisplatin. Oncotarget. 2015;6(2):1020.
15. Yang P, Liang S-X, Huang W-H, Zhang H-W, Li X-L, Xie L-H, et al. Aberrant expression of CXCR4 significantly contributes to metastasis and predicts poor clinical outcome in breast cancer. Curr Mol Med. 2014;14(1):174-84.
16. Zhao S, Wu B, Stevens RC. Advancing chemokine GPCR structure based drug discovery. Structure. 2019;27(3):405-8.
17. Zhou K, Xie L, Peng X, Guo Q, Wu Q, Wang W, et al. CXCR4 antagonist AMD3100 enhances the response of MDA-MB-231 triple-negative breast cancer cells to ionizing radiation. Cancer lett. 2018;418:196-203.
18. Hinton CV, Avraham S, Avraham HK. Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain. Clin Exp Metastasis. 2010;27:97-105.
19. Khalid M, Hussain MT, Hanif M, Qadeer G, Rama NH, Kornienko A, Khan KM. Synthesis and anti-cancer, anti-metastatic evaluation of some new fluorinated isocoumarins and 3, 4-dihydroisocoumarins. J Fluorine Chemistry. 2012;135:240-5.
20. Khorramdelazad H, Bagherzadeh K, Rahimi A, Safari E, Hassanshahi G, Khoshmirsafa M, et al. Antitumor activities of a novel fluorinated small molecule (A1) in CT26 colorectal cancer cells: molecular docking and in vitro studies. J Biomol Structure Dynamics. 2023:1-14.
21. He Y, Zhu Q, Chen M, Huang Q, Wang W, Li Q, et al. The changing 50% inhibitory concentration (IC50) of cisplatin: a pilot study on the artifacts of the MTT assay and the precise measurement of density-dependent chemoresistance in ovarian cancer. Oncotarget. 2016;7(43):70803.
22. Ke B, Tian M, Li J, Liu B, He G. Targeting programmed cell death using small‐molecule compounds to improve potential cancer therapy. Med Res Rev. 2016;36(6):983-1035.
23. Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N, Slamon DJ. Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro. Breast cancer Res Treat. 2007;105:319-26.
24. Zielińska KA, Katanaev VL. The signaling duo CXCL12 and CXCR4: Chemokine fuel for breast cancer tumorigenesis. Cancers. 2020;12(10):3071.
25. Liu T, Li X, You S, Bhuyan SS, Dong L. Effectiveness of AMD3100 in treatment of leukemia and solid tumors: from original discovery to use in current clinical practice. Exp Hematol Oncol. 2015;5:1-11.
26. Jung H, Paust S. Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy. Front Immunol. 2024;15:1443366.
27. Martins JRdS. The role of CXCR4 in cancer exosomes and metastasis 2018.
28. Mousavi A. CXCL12/CXCR4 signal transduction in diseases and its molecular approaches in targeted-therapy. Immunol Lett. 2020;217:91-115.
29. Chinni SR, Sivalogan S, Dong Z, Filho JCT, Deng X, Bonfil RD, Cher ML. CXCL12/CXCR4 signaling activates Akt‐1 and MMP‐9 expression in prostate cancer cells: the role of bone microenvironment‐associated CXCL12. Prostate. 2006;66(1):32-48.
30. Li YM, Pan Y, Wei Y, Cheng X, Zhou BP, Tan M, et al. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. Cancer cell. 2004;6(5):459-69.
31. Kittang AO, Kordasti S, Sand KE, Costantini B, Kramer AM, Perezabellan P, et al. Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome. Oncoimmunology. 2016;5(2):e1062208.
32. D'agostino G, Saporito A, Cecchinato V, Silvestri Y, Borgeat A, Anselmi L, Uguccioni M. Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration. British J Anaesthesia. 2018;121(4):962-8.
33. Lefort S, Thuleau A, Kieffer Y, Sirven P, Bieche I, Marangoni E, et al. CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancer patients. Oncogene. 2017;36(9):1211-22.
34. Xu C, Zhao H, Chen H, Yao Q. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther. 2015:4953-64.
35. Tamamura H, Hori A, Kanzaki N, Hiramatsu K, Mizumoto M, Nakashima H, et al. T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer. FEBS lett. 2003;550(1-3):79-83.
36. Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007;7(2):79-94.
37. Cavnar S, Ray P, Moudgil P, Chang S, Luker K, Linderman J, et al. Microfluidic source-sink model reveals effects of biophysically distinct CXCL12 isoforms in breast cancer chemotaxis. Integrative Biol. 2014;6(5):564-76.
38. Hirbe AC, Rubin J, Uluçkan Ö, Morgan EA, Eagleton MC, Prior JL, et al. Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone. Proc Natl Acad Sci U S A. 2007;104(35):14062-7.
39. Larochelle A, Krouse A, Metzger M, Orlic D, Donahue RE, Fricker S, et al. AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates. Blood. 2006;107(9):3772-8.
40. Luo Z, Wang B, Chen Y, Liu H, Shi L. Novel CXCR4 Inhibitor CPZ1344 Inhibits the Proliferation, Migration and Angiogenesis of Glioblastoma. Pathol Oncol Res. 2020;26:2597-604.
41. Leelawat K, Keeratichamroen S, Leelawat S, Tohtong R. CD24 induces the invasion of cholangiocarcinoma cells by upregulating CXCR4 and increasing the phosphorylation of ERK1/2. Oncol lett. 2013;6(5):1439-46.
42. Mayr C, Neureiter D, Pichler M, Berr F, Wagner A, Kiesslich T, Namberger K. Cytotoxic effects of chemokine receptor 4 inhibition by AMD3100 in biliary tract cancer cells: Potential drug synergism with gemcitabine. Mol Med Rep. 2015;12(2):2247-52.
43. Berghuis D, Schilham MW, Santos SJ, Savola S, Knowles HJ, Dirksen U, et al. The CXCR4-CXCL12 axis in Ewing sarcoma: promotion of tumor growth rather than metastatic disease. Clin Sarcoma Res. 2012;2:1-9.
44. Liao Y-X, Fu Z-Z, Zhou C-H, Shan L-C, Wang ZY, Yin F, et al. AMD3100 reduces CXCR4-mediated survival and metastasis of osteosarcoma by inhibiting JNK and Akt, but not p38 or Erk1/2, pathways in in vitro and mouse experiments. Oncol Rep. 2015;34(1):33-42.
45. Qiu J, Zhao B, Shen Y, Chen W, Ma Y, Shen Y. A novel p-terphenyl derivative inducing cell-cycle arrest and apoptosis in MDA-MB-435 cells through topoisomerase inhibition. Europ J Med Chemistry. 2013;68:192-202.
46. Goodell JR, Ougolkov AV, Hiasa H, Kaur H, Remmel R, Billadeau DD, Ferguson DM. Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis. J Med Chemistry. 2008;51(2):179-82.
47. Morein D, Erlichman N, Ben-Baruch A. Beyond cell motility: the expanding roles of chemokines and their receptors in malignancy. Front Immunol. 2020;11:952.
48. McConnell AT. Implications of MEK and VEGFR2 inhibition on melanoma CXCR4-CXCL12 chemotaxis, survival and tumour progression: Newcastle University; 2017.
49. Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863(12):2977-92.
50. Esmaeili MA, Farimani MM, Kiaei M. Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS-mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2) cells. Mol Cell Biochemistry. 2014;397:17-31.
51. Löbrich M, Jeggo PA. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Na Rev Cancer. 2007;7(11):861-9.
52. Wang F-Z, Fei H-r, Cui Y-J, Sun Y-K, Li Z-M, Wang X-Y, et al. The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Apoptosis. 2014;19:1389-98.
53. Balkwill F, editor The significance of cancer cell expression of the chemokine receptor CXCR4. Seminars Cancer Biol; 2004: Elsevier.
54. Darash-Yahana M, Pikarsky E, Abramovitch R, Zeira E, Pal B, Karplus R, et al. Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. FASEB J. 2004;18(11):1240-2.
55. Ishikawa T, Nakashiro K-I, Klosek SK, Goda H, Hara S, Uchida D, Hamakawa H. Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma. Oncol Reports. 2009;21(3):707-12.
56. Spinello I, Quaranta M, Riccioni R, Riti V, Pasquini L, Boe A, et al. MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias. Blood Cancer J. 2011;1(6):e26-e.
57. Neel NF, Schutyser E, Sai J, Fan G-H, Richmond A. Chemokine receptor internalization and intracellular trafficking. Cytokine Growth Factor Rev. 2005;16(6):637-58.
| Files | ||
| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Breast cancer CXCR4 Fluorine Small molecule | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Rahimi A, Khorramdelazad H, Darehkordi A, Hassanshahi G, Khoshmirsafa M, Karimi M, Falak R, Safari E. Exploring the Therapeutic Potential of Fluorinated CXCR4 Inhibitor A1: Insights from Breast Cancer In Vitro Investigations. Iran J Allergy Asthma Immunol. 2025;:1-11.
