Biomolecules & Therapeutics

  • 제32권6호
  • /
  • Pages.759-766
  • /
  • 2024
  • /
  • 1976-9148(pISSN)
  • /
  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
권호 표지
DOI QR코드

DOI QR Code

Isoorientin Suppresses Invasion of Breast and Colon Cancer Cells by Inhibition of CXC Chemokine Receptor 4 Expression

  • Buyun Kim (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Byoungduck Park (College of Pharmacy, Sahmyook University)
  • 투고 : 2024.08.13
  • 심사 : 2024.09.07
  • 발행 : 2024.11.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Cancer metastasis still accounts for up to 90% of cancer-related deaths, but the molecular mechanism for metastasis is unclear. Several chemokines and their receptors mediate tumor cell metastasis, particularly through long-term effects that regulate angiogenesis, tumor cell proliferation and apoptosis. Among them, CXC chemokine receptor 4 (CXCR4) has been shown to play a pivotal role in cancer metastasis through interaction with a ligand (CXCL12), also known as stromal cell-derived factor 1α (SDF-1α). The CXCR4 promoter region is well characterized, and its expression is controlled by various transcriptional factors, including NF-κB, HIF-1α, and so forth. Isoorientin (ISO) is a 3', 4', 5, 7-tetrahydroxy-6-C-glucopyranosyl flavone. ISO has been reported to exhibit anti-oxidant, anti-cancer, and anti-inflammatory properties. However, the anti-metastatic effect of ISO following downregulation of CXCR4 is unknown, and the mechanism underlying the antitumor activity has yet to be elucidated. In our present study, we showed that ISO inhibited the expression of CXCR4 through NF-κB regulation in breast and colon cancer cells. We have also demonstrated that ISO inhibits CXCR4 expression in a variety of tumor cells. Furthermore, we found that CXCR4 expression is regulated through inhibition of the transcription process. Inhibition of CXCR4 expression also reduced the invasion of cancer cells by CXCL12. In conclusion, our results suggest that ISO is a novel inhibitor to regulate CXCR4 expression and the key molecule contributing to antitumor activity.

키워드

과제정보

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2020-KH087790).

참고문헌

  1. Boudjadi, S., Chatterjee, B., Sun, W., Vemu, P. and Barr, F. G. (2018) The expression and function of PAX3 in development and disease. Gene 666, 145-157.
  2. Bradley, C. A. (2018) CXCR4-HIF-1alpha interaction drives metastasis. Nat. Rev. Urol. 15, 726.
  3. Caballero, A., Mahn, S. A., Ali, M. S., Rogers, M. R. and Marchese, A. (2019) Heterologous regulation of CXCR4 lysosomal trafficking. J. Biol. Chem. 294, 8023-8036.
  4. Chen, P., Cai, X., Yang, Y., Chen, Z., Qiu, J., Yu, N., Tang, M., Wang, Q., Ge, J., Yu, K. and Zhuang, J. (2017) Nuclear respiratory factor-1 (NRF-1) regulates transcription of the CXC receptor 4 (CXCR4) in the rat retina. Invest. Ophthalmol. Vis. Sci. 58, 4662-4669.
  5. Chen, Z., Han, F., Du, Y., Shi, H. and Zhou, W. (2023) Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther. 8, 70.
  6. Choi, E. K., Kim, H. D., Park, E. J., Song, S. Y., Phan, T. T., Nam, M., Kim, M., Kim, D. U. and Hoe, K. L. (2023) 8-Methoxypsoralen induces apoptosis by upregulating p53 and inhibits metastasis by downregulating MMP-2 and MMP-9 in human gastric cancer cells. Biomol. Ther. (Seoul) 31, 219-226.
  7. Christian, F., Smith, E. L. and Carmody, R. J. (2016) The regulation of NF-κB subunits by phosphorylation. Cells 5, 12.
  8. Cui, T., Lan, Y., Lu, Y., Yu, F., Lin, S., Fu, Y., Qiu, J. and Niu, G. (2023) Isoorientin ameliorates H(2)O(2)-induced apoptosis and oxidative stress in chondrocytes by regulating MAPK and PI3K/Akt pathways. Aging 15, 4861-4874.
  9. Ebbing, E. A., Steins, A., Fessler, E., Stathi, P., Lesterhuis, W. J., Krishnadath, K. K., Vermeulen, L., Medema, J. P., Bijlsma, M. F. and van Laarhoven, H. W. M. (2017) Esophageal adenocarcinoma cells and xenograft tumors exposed to Erb-b2 receptor tyrosine kinase 2 and 3 inhibitors activate transforming growth factor beta signaling, which induces epithelial to mesenchymal transition. Gastroenterology 153, 63-76.e14.
  10. Ebrahimi, N., Abdulwahid, A.-H. R. R., Mansouri, A., Karimi, N., Bostani, R. J., Beiranvand, S., Adelian, S., Khorram, R., Vafadar, R., Hamblin, M. R. and Aref, A. R. (2024) Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy. Cell. Mol. Life Sci. 81, 106.
  11. Garg, P., Jallepalli, V. R. and Verma, S. (2024) Unravelling the CXCL12/CXCR4 Axis in breast cancer: insights into metastasis, microenvironment interactions, and therapeutic opportunities. Hum. Gene 40, 201272.
  12. Ge, Z., Zhang, Q., Lin, W., Jiang, X. and Zhang, Y. (2023) The role of angiogenic growth factors in the immune microenvironment of glioma. Front. Oncol. 13, 1254694.
  13. Giorgiutti, S., Rottura, J., Korganow, A. S. and Gies, V. (2024) CXCR4: from B-cell development to B cell-mediated diseases. Life Sci. Alliance 7, e202302465.
  14. Giri S., Park, G. H., Choi, J. S., Ma, E., Chun, K. S. and Joo, S. H. (2023) MS-5, a naphthalene derivative, induces apoptosis in human pancreatic cancer BxPC-3 cells by modulating reactive oxygen species. Biomol. Ther. (Seoul) 31, 68-72.
  15. Gundogdu, G., Dodurga, Y., Elmas, L., Tasci, S. Y. and Karaoglan, E. S. (2018) Investigation of the anticancer mechanism of isoorientin isolated from Eremurus spectabilis leaves via cell cycle pathways in HT-29 human colorectal adenocarcinoma cells. Eurasian J. Med. 50, 168-172.
  16. Jiang, C., Ma, S., Hu, R., Wang, X., Li, M., Tian, F., Jiang, W., Zhu, L. and Bian, Z. (2018) Effect of CXCR4 on apoptosis in osteosarcoma cells via the PI3K/Akt/NF-kappabeta signaling pathway. Cell. Physiol. Biochem. 46, 2250-2260.
  17. Khare, T., Bissonnette, M. and Khare, S. (2021) CXCL12-CXCR4/CXCR7 Axis in colorectal cancer: therapeutic target in preclinical and clinical studies. Int. J. Mol. Sci. 22, 7371.
  18. Kim, B., Kim, J. H. and Park, B. (2016) Pomolic acid inhibits invasion of breast cancer cells through the suppression of CXC chemokine receptor type 4 expression. J. Cell. Biochem. 117, 1296-1307.
  19. Kim, B., Lee, K. Y. and Park, B. (2021) Isoorientin inhibits amyloid β(25-35)-induced neuronal inflammation in BV2 cells by blocking the NF-κB signaling pathway. Molecules 26, 7056.
  20. Kim, B., Min, Y. H. and Park, B. (2020) Minecoside modulates cell invasion via regulation of CXCR4 expression in breast and colon cancer cells. Planta Med. 86, 331-337.
  21. Kim, B. and Park, B. (2014) Baohuoside I suppresses invasion of cervical and breast cancer cells through the downregulation of CXCR4 chemokine receptor expression. Biochemistry 53, 7562-7569.
  22. Kruizinga, R. C., van Marion, D. M., den Dunnen, W. F., de Groot, J. C., Hoving, E. W., Oosting, S. F., Timmer-Bosscha, H., Derks, R. P., Cornelissen, C., van der Luijt, R. B., Links, T. P., de Vries, E. G. and Walenkamp, A. M. (2016) Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma. Fam. Cancer 15, 607-616.
  23. Lee, H. H., Jeong, J. W., Hong, S. H., Park, C., Kim, B. W. and Choi, Y. H. (2018) Diallyl trisulfide suppresses the production of lipopolysaccharide-induced inflammatory mediators in BV2 microglia by decreasing the NF-kappaB pathway activity associated with toll-like receptor 4 and CXCL12/CXCR4 pathway blockade. J. Cancer Prev. 23, 134-140.
  24. Li, F., Xue, Z. Y., Yuan, Y., Huang, S. S., Fan, Y. H., Zhu, X. and Wei, L. (2018) Upregulation of CXCR4 through promoter demethylation contributes to inflammatory hyperalgesia in rats. CNS Neurosci. Ther. 24, 947-956.
  25. Liu, S. C., Huang, C. S., Huang, C. M., Hsieh, M. S., Huang, M. S., Fong, I. H., Yeh, C. T. and Lin, C. C. (2021) Isoorientin inhibits epithelial-to-mesenchymal properties and cancer stem-cell-like features in oral squamous cell carcinoma by blocking Wnt/β-catenin/STAT3 axis. Toxicol. Appl. Pharmacol. 424, 115581.
  26. Ong, W. Y., Herr, D. R., Sun, G. Y. and Lin, T. N. (2022) Anti-inflammatory effects of phytochemical components of Clinacanthus nutans. Molecules 27, 3607.
  27. Ryu, J., Kim, K.-i., Hossain, R., Lee, M., Hong, J. T., Lee, H. J. and Lee, C. J. (2023) Meclofenamate suppresses MUC5AC mucin gene expression by regulating the NF-kB signaling pathway in human pulmonary mucoepidermoid NCI-H292 cells. Biomol. Ther. (Seoul) 31, 306-311.
  28. San-Millan, I., Martinez, J. L., Pickard, S. L., Yu, H., Hirsch, F. R., Rivard, C. J. and Brooks, G. A. (2023) Role of lactate in the regulation of transcriptional activity of breast cancer-related genes and epithelial-to-mesenchymal transition proteins: a compassion of MCF7 and MDA-MB-231 cancer cell lines. bioRxiv doi: 10.1101/2023.03.23.533060 [Preprint].
  29. Shi, Y. X., Liu, C. X., Liu, F., Zhang, H. M., Yu, M. M., Jin, Y. H., Shang, S. M. and Fu, Y. X. (2020) Efficacy of adherence-enhancing interventions for immunosuppressive therapy in solid organ transplant recipients: a systematic review and meta-analysis based on randomized controlled trials. Front. Pharmacol. 11, 578887.
  30. Ullah, A., Chen, Y., Singla, R. K., Cao, D. and Shen, B. (2024) Proinflammatory cytokines and CXC chemokines as game-changer in age-associated prostate cancer and ovarian cancer: Insights from preclinical and clinical studies' outcomes. Pharmacol. Res. 204, 107213.
  31. Vitale, I., Pietrocola, F., Guilbaud, E., Aaronson, S. A., Abrams, J. M., Adam, D., Agostini, M., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., Aqeilan, R. I., Arama, E., Baehrecke, E. H., Balachandran, S., Bano, D., Barlev, N. A., Bartek, J., Bazan, N. G., Becker, C., Bernassola, F., Bertrand, M. J. M., Bianchi, M. E., Blagosklonny, M. V., Blander, J. M., Blandino, G., Blomgren, K., Borner, C., Bortner, C. D., Bove, P., Boya, P., Brenner, C., Broz, P., Brunner, T., Damgaard, R. B., Calin, G. A., Campanella, M., Candi, E., Carbone, M., Carmona-Gutierrez, D., Cecconi, F., Chan, F. K. M., Chen, G.-Q., Chen, Q., Chen, Y. H., Cheng, E. H., Chipuk, J. E., Cidlowski, J. A., Ciechanover, A., Ciliberto, G., Conrad, M., Cubillos-Ruiz, J. R., Czabotar, P. E., D'Angiolella, V., Daugaard, M., Dawson, T. M., Dawson, V. L., De Maria, R., De Strooper, B., Debatin, K.-M., Deberardinis, R. J., Degterev, A., Del Sal, G., Deshmukh, M., Di Virgilio, F., Diederich, M., Dixon, S. J., Dynlacht, B. D., ElDeiry, W. S., Elrod, J. W., Engeland, K., Fimia, G. M., Galassi, C., Ganini, C., Garcia-Saez, A. J., Garg, A. D., Garrido, C., Gavathiotis, E., Gerlic, M., Ghosh, S., Green, D. R., Greene, L. A., Gronemeyer, H., Hacker, G., Hajnoczky, G., Hardwick, J. M., Haupt, Y., He, S., Heery, D. M., Hengartner, M. O., Hetz, C., Hildeman, D. A., Ichijo, H., Inoue, S., Jaattela, M., Janic, A., Joseph, B., Jost, P. J., Kanneganti, T.-D., Karin, M., Kashkar, H., Kaufmann, T., Kelly, G. L., Kepp, O., Kimchi, A., Kitsis, R. N., Klionsky, D. J., Kluck, R., Krysko, D. V., Kulms, D., Kumar, S., Lavandero, S., Lavrik, I. N., Lemasters, J. J., Liccardi, G., Linkermann, A., Lipton, S. A., Lockshin, R. A., Lopez-Otin, C., Luedde, T., MacFarlane, M., Madeo, F., Malorni, W., Manic, G., Mantovani, R., Marchi, S., Marine, J.-C., Martin, S. J., Martinou, J.-C., Mastroberardino, P. G., Medema, J. P., Mehlen, P., Meier, P., Melino, G., Melino, S., Miao, E. A., Moll, U. M., Munoz-Pinedo, C., Murphy, D. J., Niklison-Chirou, M. V., Novelli, F., Nunez, G., Oberst, A., Ofengeim, D., Opferman, J. T., Oren, M., Pagano, M., Panaretakis, T., Pasparakis, M., Penninger, J. M., Pentimalli, F., Pereira, D. M., Pervaiz, S., Peter, M. E., Pinton, P., Porta, G., Prehn, J. H. M., Puthalakath, H., Rabinovich, G. A., Rajalingam, K., Ravichandran, K. S., Rehm, M., Ricci, J.-E., Rizzuto, R., Robinson, N., Rodrigues, C. M. P., Rotblat, B., Rothlin, C. V., Rubinsztein, D. C., Rudel, T., Rufini, A., Ryan, K. M., Sarosiek, K. A., Sawa, A., Sayan, E., Schroder, K., Scorrano, L., Sesti, F., Shao, F., Shi, Y., Sica, G. S., Silke, J., Simon, H.-U., Sistigu, A., Stephanou, A., Stockwell, B. R., Strapazzon, F., Strasser, A., Sun, L., Sun, E., Sun, Q., Szabadkai, G., Tait, S. W. G., Tang, D., Tavernarakis, N., Troy, C. M., Turk, B., Urbano, N., Vandenabeele, P., Vanden Berghe, T., Vander Heiden, M. G., Vanderluit, J. L., Verkhratsky, A., Villunger, A., von Karstedt, S., Voss, A. K., Vousden, K. H., Vucic, D., Vuri, D., Wagner, E. F., Walczak, H., Wallach, D., Wang, R., Wang, Y., Weber, A., Wood, W., Yamazaki, T., Yang, H.-T., Zakeri, Z., Zawacka-Pankau, J. E., Zhang, L., Zhang, H., Zhivotovsky, B., Zhou, W., Piacentini, M., Kroemer, G. and Galluzzi, L. (2023) Apoptotic cell death in disease-current understanding of the NCCD 2023. Cell Death Differ. 30, 1097-1154.
  32. Wang, J., Wang, H., Cai, J., Du, S., Xin, B., Wei, W., Zhang, T. and Shen, X. (2018a) Artemin regulates CXCR4 expression to induce migration and invasion in pancreatic cancer cells through activation of NF-kappaB signaling. Exp. Cell Res. 365, 12-23.
  33. Wang, W., Nag, S. A. and Zhang, R. (2015) Targeting the NFκB signaling pathways for breast cancer prevention and therapy. Curr. Med. Chem. 22, 264-289.
  34. Wang, Z., Ma, Y., Yu, X., Niu, Q., Han, Z., Wang, H., Li, T., Fu, D., Achilefu, S., Qian, Z. and Gu, Y. (2018b) Targeting CXCR4-CXCL12 axis for visualizing, predicting, and inhibiting breast cancer metastasis with theranostic AMD3100-Ag2S quantum dot probe. 28, 1800732.
  35. Xu, C., Zheng, L., Li, D., Chen, G., Gu, J., Chen, J. and Yao, Q. (2018) CXCR4 overexpression is correlated with poor prognosis in colorectal cancer. Life Sci. 208, 333-340.
  36. Yang, Y., Li, J., Lei, W., Wang, H., Ni, Y., Liu, Y., Yan, H., Tian, Y., Wang, Z., Yang, Z., Yang, S., Yang, Y. and Wang, Q. (2023) CXCL12-CXCR4/CXCR7 axis in cancer: from mechanisms to clinical applications. Int. J. Biol. Sci. 19, 3341-3359.
  37. Ye, T., Su, J., Huang, C., Yu, D., Dai, S., Huang, X., Chen, B. and Zhou, M. (2016) Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells. Onco Targets Ther. 9, 7481-7492.
  38. Yuan, L., Wang, J., Wu, W., Liu, Q. and Liu, X. (2016) Effect of isoorientin on intracellular antioxidant defence mechanisms in hepatoma and liver cell lines. Biomed. Pharmacother. 81, 356-362.
  39. Yuan, L., Wei, S., Wang, J. and Liu, X. (2014) Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. J. Agric. Food Chem. 62, 5390-5400.
  40. Yue, M., Chen, M. M., Zhang, B., Wang, Y., Li, P. and Zhao, Y. (2024) The functional roles of chemokines and chemokine receptors in colorectal cancer progression. Biomed. Pharmacother. 170, 116040.
  41. Zielinska, K. A. and Katanaev, V. L. (2020) The signaling duo CXCL12 and CXCR4: chemokine fuel for breast cancer tumorigenesis. Cancers (Basel) 12, 3071.