Poly-guanidine shows high cytotoxicity in glioma cell cultures and glioma stem cells
Tóm tắt
Glioblastoma multiforme (GBM) is a malignant CNS tumor with a poor prognosis. GBM shows aberrant glycosylation with hypersialylation. This property is a potential target for therapy. This study investigates the growth inhibitory efficacy of poly-guanidine (GuaDex), with an affinity for sialic acid (Sia). Glioma cell cultures and patient-derived glioma cell lines (PDGCLs) expressing Prominin-1 (CD133) were used. Human fibroblasts and astrocyte-derived cells were used as controls. Temozolomide (standard GBM drug, TMZ) and DMSO were used as a comparison. GuaDex at 1–10 µM concentrations, were incubated for 3.5–72 h and with PDGCLs cells for 6–24 h. The cytotoxicity was estimated with a fluorometric cytotoxicity assay (FMCA). Fluorescence-labelled GuaDex was used to study the cell interactions. Sia expression was confirmed with a fluorescence labelled Sia binding lectin. Expression of glial fibrillary acidic protein was determined. GuaDex induction of growth inhibition was fast, showing after less than 5 min incubation while the control cells were not affected even after 50 min incubation. The growth inhibitory effect on PDGCLs spheroids was persistent still showing after 4 weeks post-treatment. The growth inhibition of GuaDex was induced at low µM concentrations while TMZ induced only a slight inhibition at mM concentrations. GuaDex efficacy appears significant and warrants further studies.
Tài liệu tham khảo
Hanif F, Muzaffar K, Perveen K et al (2017) Glioblastoma Multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev 18(1):3–9
Lara-Velazquez M, Al-Kharboosh R, Jeanneret S et al (2017) Advances in brain tumor surgery for glioblastoma in adults. Brain Sci 7(12):166
Sharif Y, Jumah F, Coplan L et al (2018) Blood brain barrier: a review of its anatomy and physiology in health and disease. Clin Anat 31(6):812–823
Dréan A, Goldwirt L, Verreault M et al (2016) Blood-brain barrier, cytotoxic chemotherapies and Glioblastoma. Expert Rev Neurother 16(11):1285–1300
Newlands ES, Stevens MF, Wedge SR et al (1997) Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev 23(1):35–61
Büll C, Stoel MA, den Brok MH et al (2014) Sialic acids sweeten a tumor’s life. Cancer Res 74(12):3199–3204
Fonseca LM, Silva VA, Freire-de-Lima L et al (2016) Glycosylation in cancer: interplay between multidrug resistance and epithelial-to-mesenchymal transition. Front Oncol 6:158
Holmberg AR, Wilchek M, Márquez M et al (1999) Ion exchange tumor targeting: A new approach. Clin Cancer Res 5:3056s–3058s
Meurling L, Márquez M, Nilsson S et al (2009) Polymer-conjugated guanidine is a potentially useful anti-tumor agent. Int J Oncol 35:281–285
Kroemer G, Pouyssegur J (2008) Tumor cell metabolism. Cancer Cell 13(6):472–482
Nowotarski SL, Woster PM, Casero RA Jr (2013) Polyamines and cancer: Implications for chemoprevention and chemotherapy. Expert Rev Mol Med 15:e3. https://doi.org/10.1017/erm.2013.3
Larsson R, Nygren P (1989) A rapid fluorometric method for semi-automated determination of cytotoxicity and cellular proliferation of human tumor cell lines in microculture. Anticancer Res 9:1111–1119
Piccinini F, Tesei A, Arienti C et al (2017) Cell counting and viability assessment of 2D and 3D cell cultures: excepted reliability of the trypan blue assay. Biol Proced Online 19:8. https://doi.org/10.1186/s12575-017-0056-3
Sirenko O, Mitlo T, Hesley J et al (2015) High-content assays for characterizing the viability and morphology of 3D cancer spheroids cultures. Assay Drug Dev Technol 13(7):402–414
Singh M, Close DA, Mukundan S et al (2015) Production of uniform 3D microtumors in hydrogel microwell arrays for measurement of viability, morphology, and signaling pathway activation. Assay Drug Dev Technol 13(9):570–583
Cai X, Sughrue ME (2018) Glioblastoma: new therapeutic strategies to address cellular and genomic complexity. Oncotarget 9(10):9540–9554
De Felice F, Musio D, Cassese R, Gravina GL, Tombolini V (2017) New approaches in Glioblastoma multiforme; the potential role of immune-check point inhibitors. Curr Cancer Drug Targets 17(3):282–289
Ozdemir-Kaynak E, Qutub AA, Yesil-Celiktas O (2018) Advances in Glioblastoma multiforme treatment: new models for nanoparticle therapy. Front Physiol 9:170. https://doi.org/10.3389/fphys.2018.00170
Kirson ED, Gurvich Z, Schneiderman R et al (2004) Disruption of cancer cell replication by alternating electric fields. Cancer Res 64:3288–3295
Sarkaria JN, Hu LS, Parney IF et al (2018) Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro-Oncol 20(2):184–191
Butler D (2008) Translational research: crossing the valley of death. Nature 453(7197):840–842
Mak IWY, Evaniew N, Ghert M (2014) Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res 6(2):114–118
Ogi C, Aruga A (2013) Immunological monitoring of anticancer vaccines in clinical trials. Oncoimmunology 2(8):e26012. https://doi.org/10.4161/onci.26012
DiMasi JA, Grabowski HG, Hansen RA (2016) Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ 47:20–33
Munoz C (2014) The price of failure. The Economist. https://www.economist.com/business/2014/11/27/the-price-of-failure. Accessed 15 Feb 2021
Branter J, Basu S, Smith S (2018) Tumour treating fields in a combinational therapeutic approach. Oncotarget 9(93):36631–36644
Gurtovenko AA, Anwar J (2007) Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide. J Phys Chem 111(35):10453–10460
Chaichana KL, Zaidi H, Pendleton C et al (2011) The efficacy of carmustine wafers for older patients with Glioblastoma multiforme: prolonging survival. Neurol Res 33(7):759–764
Perry J, Chambers A, Spithoff K et al (2007) Gliadel wafers in the treatment of malignant glioma: a systematic review. Curr Oncol 14(5):189–194
De Bonis P, Anile C, Pompucci A et al (2013) The influence of surgery on recurrence pattern of glioblastoma. Clin Neurol Neurosurg 115(1):37–43
Nicholson C (2001) Diffusion and related transport mechanisms in brain tissue. Rep Prog Phys 64(7):815–884
Nicholson C, Hrabětová S (2017) Brain extracellular space: the final frontier of neuroscience. Biophys J 113(10):2133–2142
Escamilla-García E, Alcázar-Pizaña AG, Segoviano-Ramírez JC et al (2017) Antimicrobial activity of a cationic guanidine compound against two pathogenic oral bacteria. Int J Microbiol 2017:5924717
Li D, Liu X, Liu T et al (2020) Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes. Glia 68(5):878–897
Kummar S, Rubinstein L, Kinders R et al (2008) Phase 0 clinical trials: conceptions and misconceptions. Cancer J 14(3):133–137
Westermark B, Pontén J, Hugosson R (1973) Determinants for the establishment of permanent tissue culture lines from human gliomas. Acta Path Microbiol Scand 81(6):791–805
Westermark B (1973) The deficient density-dependent growth control of human malignant glioma cells and virus-transformed glia-like cells in culture. Int J Cancer 12(2):438–451
Bongcam-Rudloff E, Nistér M, Betsholtz C, Wang JL, Stenman G, Huebner K et al (1991) Human glial fibrillary acidic protein: complementary DNA cloning, chromosome localization, and messenger RNA expression in human glioma cell lines of various phenotypes. Cancer Res 51:1553–1560
Bigner DD, Bigner SH, Pontén J et al (1981) Heterogeneity of Genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropath Exp Neurol 40(3):201–229
Nistér M, Libermmann TA, Betsholtz C et al (1988) Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-alpha and their receptors in human malignant glioma cell lines. Cancer Res 48:3910–3918
Nistér M, Heldin CH, Westermark, (1986) Clonal variation in the production of a platelet-derived growth factor-like protein and expression of corresponding receptors in a human malignant glioma. Cancer Res 46:332–340
Mehta S, Huillard E, Kesari S et al (2011) The central nervous system-restricted transcription factor olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma. Cancer Cell 19(3):359–371
Holmberg Olausson K, Maire CL, Haidar S, Ling J et al (2014) Prominin-1 (CD133) defines both stem and non-stem cell populations in CNS development and gliomas. PLoS ONE 9(9):e106694. https://doi.org/10.1371/journal.pone.0106694
Stevens MM, Maire CL, Chou N, Murakami MA, Knoff DS, Kikuchi Y et al (2016) Drug sensitivity of single cancer cells in predicted by changes in mass accumulation rate. Nat Biotech 34(11):1161–1167