The inhibitory effect of indisulam-coumarin combined therapy on glioblastoma multiforme

Year 2023, Volume: 4 Issue: 3, 125 - 131, 30.12.2023

Fatma Şayan Poyraz , Zeynep Yağmur Karagülleoğlu , Banu Mansuroğlu

https://doi.org/10.51753/flsrt.1287232

Abstract

Cancer is a disease that occurs due to irregular growth and proliferation of body cells and can be caused by many factors. One of these factors is carbonic anhydrase 9 (CAIX). While its expression is high in malignant cells, it is a molecule whose presence is difficult to detect in healthy tissues. Glioblastoma multiforme (GBM) is one of the fast-spreading brain cancers, and unlike healthy tissues, overexpressed CAIX in its cell receptors. Indisulam, one of the new-generation drug candidates for the treatment of solid tumours, is a type of CAIX inhibitor that affects cell division progression in human tumour cells. Similarly, it is known that coumarin, as one of the new-generation drugs in cancer treatment, is used together with chemotherapy. In this study, combined treatment of indisulam and coumarin was investigated on glioblastoma multiforme cells to evaluate their cytotoxicity, cell migration and antiproliferative effects. The effects of combined treatment on cell migration and proliferation were investigated with the IC50 values determined after the cytotoxicity test. As a result of the wound healing assay, it was determined that the control cells were closed by 69.6%, while the combined treatment closed the wound by 32% and seriously prevented cell migration. The percentage of proliferative cell nuclear antigen (PCNA) positive cells decreased significantly after combined treatment, cell proliferation was 93% in the control group and 77% in the combined treatment group.

Keywords

Cancer, carbonic anhydrase IX, coumarin, indisulam, glioblastoma

Project Number

1919B012001045

References

• Abel, S. D., & Baird, S. K. (2018). Honey is cytotoxic towards prostate cancer cells but interacts with the MTT reagent: Considerations for the choice of cell viability assay. Food Chemistry, 241, 70-78.
• Baur, M., Gneist, M., Owa, T., & Dittrich, C. (2007). Clinical complete long-term remission of a patient with metastatic malignant melanoma under therapy with indisulam (E7070). Melanoma Research, 17(5), 329-331.
• Bhattacharyya, S. S., Paul, S., Dutta, S., Boujedaini, N., & Khuda-Bukhsh, A. R. (2010). Anti-oncogenic potentials of a plant coumarin (7-hydroxy-6-methoxy coumarin) against 7, 12-dimethylbenz [a] anthracene-induced skin papilloma in mice: the possible role of several key signal proteins. Zhong xi yi jie he xue bao = Journal of Chinese Integrative Medicine, 8(7), 645-654.
• Bussiere, D. E., Xie, L., Srinivas, H., Shu, W., Burke, A., Be, C., ... & Paulk, J. (2020). Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex. Nature Chemical Biology, 16(1), 15-23.
• Chahal, V., & Kakkar, R. (2023). A combination strategy of structure-based virtual screening, MM-GBSA, cross docking, molecular dynamics and metadynamics simulations used to investigate natural compounds as potent and specific inhibitors of tumour linked human carbonic anhydrase IX. Journal of Biomolecular Structure & Dynamics, 41(12), 5465-5480.
• Chahal, V., Nirwan, S., Pathak, M., & Kakkar, R. (2022). Identification of potent human carbonic anhydrase IX inhibitors: a combination of pharmacophore modeling, 3D-QSAR, virtual screening and molecular dynamics simulations. Journal of Biomolecular Structure & Dynamics, 40(10), 4516-4531.
• Chuang, J. Y., Huang, Y. F., Lu, H. F., Ho, H. C., Yang, J. S., Li, T. M., ... & Chung, J. G. (2007). Coumarin induces cell division arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria-and caspase-3 dependent mechanism and NF-κB down-regulation. In Vivo, 21(6), 1003-1009.
• Cuffaro, D., Nuti, E., & Rossello, A. (2020). An overview of carbohydrate-based carbonic anhydrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 35(1), 1906-1922.
• Feitelson, M. A., Arzumanyan, A., Kulathinal, R. J., Blain, S. W., Holcombe, R. F., Mahajna, J., ... & Nowsheen, S. (2015). Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. In Seminars in Cancer Biology. Academic Press. 35, 25-54.
• Finn, G. J., Kenealy, E., Creaven, B. S., & Egan, D. A. (2002). In vitro cytotoxic potential and mechanism of action of selected coumarins, using human renal cell lines. Cancer Letters, 183(1), 61-68.
• Fukuoka, K., Usuda, J., Iwamoto, Y., Fukumoto, H., Nakamura, T., Yoneda, T., ... & Nishio, K. (2001). Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell division progression in human non-small cell lung cancer cells. Investigational New Drugs, 19, 219-227.
• Gatenby, R. A., & Gillies, R. J. (2004). Why do cancers have high aerobic glycolysis?. Nature Reviews Cancer, 4(11), 891-899.
• Giakoumettis, D., Kritis, A., & Foroglou, N. (2018). C6 cell line: The gold standard in glioma research. Hippokratia, 22(3), 105.
• Gkionis, L., Kavetsou, E., Kalospyros, A., Manousakis, D., Garzon Sanz, M., Butterworth, S., ... & Tirella, A. (2021). Investigation of the cytotoxicity of bioinspired coumarin analogues towards human breast cancer cells. Molecular Diversity, 25, 307-321.
• Hanif, F., Muzaffar, K., Perveen, K., Malhi, S. M., & Simjee, S. U. (2017). Glioblastoma multiforme: a review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pacific Journal of Cancer Prevention: APJCP, 18(1), 3.
• Imani, A., Maleki, N., Bohlouli, S., Kouhsoltani, M., Sharifi, S., & Maleki Dizaj, S. (2021). Molecular mechanisms of anticancer effect of rutin. Phytotherapy Research, 35(5), 2500-2513.
• Ismail, R. S., El Kerdawy, A. M., Soliman, D. H., Georgey, H. H., Abdel Gawad, N. M., Angeli, A., & Supuran, C. T. (2023). Discovery of a new potent oxindole multi-kinase inhibitor among a series of designed 3-alkenyl-oxindoles with ancillary carbonic anhydrase inhibitory activity as antiproliferative agents. BMC chemistry, 17(1), 81.
• Jonkman, J. E., Cathcart, J. A., Xu, F., Bartolini, M. E., Amon, J. E., Stevens, K. M., & Colarusso, P. (2014). An introduction to the wound healing assay using live-cell microscopy. Cell Adhesion & Migration, 8(5), 440-451.
• Karcher, S., Steiner, H. H., Ahmadi, R., Zoubaa, S., Vasvari, G., Bauer, H., ... & Herold‐Mende, C. (2006). Different angiogenic phenotypes in primary and secondary glioblastomas. International Journal of Cancer, 118(9), 2182-2189.
• Kroemer, G., & Pouyssegur, J. (2008). Tumour cell metabolism: cancer's Achilles' heel. Cancer Cell, 13(6), 472-482.
• Lam, P. Y. P., di Tomaso, E., Ng, H. K., Pang, J. C. S., Roussel, M. F., & Hjelm, N. M. (2000). Expression of p19 INK4d, CDK4, CDK6 in glioblastoma multiforme. British Journal of Neurosurgery, 14(1), 28-32.
• Li, K., Wu, L., Chen, Y., Li, Y., Wang, Q., Li, M., Wang, Z. (2020). Cytotoxic and antiproliferative effects of β-mangostin on rat C6 glioma cells depend on oxidative stress induction via PI3K/AKT/mTOR pathway inhibition. Drug Design, Development and Therapy, 5315-5324.
• Lee, S., Sivakumar, K., Shin, W. S., Xie, F., & Wang, Q. (2006). Synthesis and anti-angiogenesis activity of coumarin derivatives. Bioorganic & Medicinal Chemistry Letters, 16(17), 4596-4599.
• Matsumoto, K., Moriuchi, T., Koji, T., & Nakane, P. K. (1987). Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin. The EMBO Journal, 6(3), 637-642.
• Moncao, C. C. D., Scrideli, C. A., Andrade, A. F., Viapiano, M. S., Carlotti, C. G., Moreno, D. A., Baroni, M., Tone, L. G., & Teixeira, S. A. (2022). Indisulam reduces viability and regulates apoptotic gene expression in pediatric high-grade glioma cells. Biomedicines, 11(1), 68.
• Oda, Y., Owa, T., Sato, T., Boucher, B., Daniels, S., Yamanaka, H., ... & Nagasu, T. (2003). Quantitative chemical proteomics for identifying candidate drug targets. Analytical Chemistry, 75(9), 2159-2165.
• Ozawa, Y., Sugi, N. H., Nagasu, T., Owa, T., Watanabe, T., Koyanagi, N., ... & Yoshimatsu, K. (2001). E7070, a novel sulphonamide agent with potent antitumour activity in vitro and in vivo. European Journal of Cancer, 37(17), 2275-2282.
• Pontecorvi, V., Mori, M., Picarazzi, F., Zara, S., Carradori, S., Cataldi, A., ... & Supuran, C. T. (2022). Novel Insights on Human Carbonic Anhydrase Inhibitors Based on Coumalic Acid: Design, Synthesis, Molecular Modeling Investigation, and Biological Studies. International Journal of Molecular Sciences, 23(14), 7950.
• Prelich, G., Tan, C. K., Kostura, M., Mathews, M. B., So, A. G., Downey, K. M., & Stillman, B. (1987). Functional identity of proliferating cell nuclear antigen and a DNA polymerase-δ auxiliary protein. Nature, 326(6112), 517-520.
• Robert, M. C., & Wastie, M. L. (2008). Glioblastoma multiforme: a rare manifestation of extensive liver and bone metastases. Biomedical Imaging and Intervention Journal, 4(1).
• Rodriguez, L. G., Wu, X., & Guan, J. L. (2005). Wound-healing assay. Cell Migration: Developmental Methods and Protocols, 23-29.
• Sayed, A. M., Saleh, N. M., El‐Gaby, M. S., Abdel‐Samad, M. R., & Taher, F. A. (2021). Synthesis and in vivo evaluation of novel benzimidazole‐sulfonamide hybrids and Lucilia cuprina maggots' excretion/secretion topical gels for wound healing. Journal of the Chinese Chemical Society, 68(7), 1291-1301.
• Strzalka, W., & Ziemienowicz, A. (2011). Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell division regulation. Annals of botany, 107(7), 1127-1140.
• Stubbs, M., McSheehy, P. M., Griffiths, J. R., & Bashford, C. L. (2000). Causes and consequences of tumour acidity and implications for treatment. Molecular Medicine Today, 6(1), 15-19.
• Sumorek-Wiadro, J., Zając, A., Langner, E., Skalicka-Woźniak, K., Maciejczyk, A., Rzeski, W., & Jakubowicz-Gil, J. (2020). Antiglioma potential of coumarins combined with Sorafenib. Molecules, 25(21), 5192.
• Supuran, C. T. (2003). Indisulam: an anticancer sulfonamide in clinical development. Expert Opin Investig Drugs, 12(2), 283-287.
• Teixeira, S. A., Viapiano, M. S., Andrade, A. F., Nandhu, M. S., Pezuk, J. A., Bidinotto, L. T., ... & Scrideli, C. A. (2021). The carbonic anhydrase inhibitor E7070 sensitizes glioblastoma cells to radio-and chemotherapy and reduces tumour growth. Molecular Neurobiology, 58(9), 4520-4534.
• Touisni, N., Maresca, A., McDonald, P. C., Lou, Y., Scozzafava, A., Dedhar, S., ... & Supuran, C. T. (2011). Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumours. Journal of Medicinal Chemistry, 54(24), 8271-8277.
• Wang, X., Decker, C. C., Zechner, L., Krstin, S., & Wink, M. (2019). In vitro wound healing of tumour cells: inhibition of cell migration by selected cytotoxic alkaloids. BMC Pharmacology and Toxicology, 20(1), 1-12.
• Welder, A. A., Grant, R., Bradlaw, J., & Acosta, D. (1991). A primary culture system of adult rat heart cells for the study of toxicologic agents. In vitro Cellular & Developmental Biology-Animal, 27, 921-926.
• Yu, Y. L., Chou, R. H., Liang, J. H., Chang, W. J., Su, K. J., Tseng, Y. J., ... & Hung, M. C. (2013). Targeting the EGFR/PCNA signaling suppresses tumour growth of triple-negative breast cancer cells with cell-penetrating PCNA peptides. PLoS One, 8(4), e61362.