Document Type : Original paper
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background and Objectives: Macrophages play an important role in tumor growth (M2 macrophage) or suppression (M1 macrophage). Auraptene, a prenyloxycoumarin compound extracted from Citrus plants, has anti-cancer and anti-inflammatory properties. The purpose of this study was to look into the effect of auraptene on macrophage polarization and the tumor microenvironment when a human monocyte cell line (THP-1) was co-cultured with human colorectal adenocarcinoma (HT-29). Methods: The toxicity of auraptene on THP-1 and HT-29 cells was determined by the MTT method. Using flow cytometry, the effect of auraptene on macrophage polarization was studied through THP-1 as a macrophage source. The effect of auraptene on the macrophage population was also studied in THP-1 co-cultured with HT-29. Furthermore, macrophage function was assessed by measuring IL-10 and IL-12 concentrations using the ELISA method, nitric oxide (NO) concentrations using the Griess method, and HT-29 apoptosis by flow cytometry. Results: The M1/M2 ratio of THP-1 exposed to auraptene increased significantly in both naive THP-1 and THP-1 co-cultured with HT-29. Auraptene significantly reduced tumor-protective IL-10 secretion in M1 (p=0.0032) and M2 (p=0.0011). Auraptene increased anti-tumor IL-12 in M2 significantly (p=0.0011). It increased M1 NO production (p=0.0236) while decreasing M2 NO production (p=0.0001). Auraptene also increased HT-29 apoptosis in M0 and M1 co-cultures (p<0.0001). Conclusion: Auraptene altered the release profiles and macrophage types to enhance the suppression of HT-29 cells.