Basson, CharlisePhiri, Avulundiah EdwinGandhi, ManjunathAnguelov, RoumenSerem, June CheptooBipath, PriyeshHlophe, Yvette Nkondo2024-05-152024-05-152024-06Basson, C., Phiri, A.E., Gandhi, M., et al. In vitro effects and mathematical modelling of CTCE-9908 (a chemokine receptor 4 antagonist) on melanoma cell survival. Clinical and Experimental Pharmacology and Physiology 2024; 51(6): e13865. doi: 10.1111/1440-1681.13865.0305-1870 (print)1440-1681 (online)10. 1111/1440-1681.13865http://hdl.handle.net/2263/95973DATA AVAILABILITY STATEMENT : The dataset(s) supporting the conclusions of this article is(are) included within the article.CTCE-9908, a CXC chemokine receptor 4 (CXCR4) antagonist, prevents CXCR4 phosphorylation and inhibits the interaction with chemokine ligand 12 (CXCL12) and downstream signalling pathways associated with metastasis. This study evaluated the in vitro effects of CTCE-9908 on B16 F10 melanoma cells with the use of mathematical modelling. Crystal violet staining was used to construct a mathematical model of CTCE-9908 B16 F10 (melanoma) and RAW 264.7 (non-cancerous macrophage) cell lines on cell viability to predict the half-maximal inhibitory concentration (IC50). Morphological changes were assessed using transmission electron microscopy. Flow cytometry was used to assess changes in cell cycle distribution, apoptosis via caspase-3, cell survival via extracellular signal-regulated kinase1/2 activation, CXCR4 activation and CXCL12 expression. Mathematical modelling predicted IC50 values from 0 to 100 h. At IC50, similar cytotoxicity between the two cell lines and ultrastructural morphological changes indicative of cell death were observed. At a concentration 10 times lower than IC50, CTCE-9908 induced inhibition of cell survival (p = 0.0133) in B16 F10 cells but did not affect caspase-3 or cell cycle distribution in either cell line. This study predicts CTCE-9908 IC50 values at various time points using mathematical modelling, revealing cytotoxicity in melanoma and non-cancerous cells. CTCE-9908 significantly inhibited melanoma cell survival at a concentration 10 times lower than the IC50 in B16 F10 cells but not RAW 264.7 cells. However, CTCE-9908 did not affect CXCR4 phosphorylation, apoptosis,\ or cell cycle distribution in either cell line.en© 2024 The Authors. Clinical and Experimental Pharmacology and Physiology published by John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.Cell survivalCTCE-9908CXC chemokine receptor 4 (CXCR4)Mathematical modellingMelanomaChemokine ligand 12 (CXCL12)Health sciences articles SDG-03SDG-03: Good health and well-beingArticle