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

doi:10.18502/ijaai.v24i5.19748

Ali Rahimi Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Hossein Khorramdelazad Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Ali Darehkordi Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran
Gholamhossein Hassanshahi Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Majid Khoshmirsafa Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Milad Karimi Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Reza Falak Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Elaheh Safari Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v24i5.19748

Keywords: Breast cancer; CXCR4; Fluorine; Small molecule

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.