Macrophage-Driven Antitumor and Antimetastatic Activity of an Arabinogalactan from Anadenanthera colubrina
Dakson D. Araújo, Valdenizia R. Silva, Luciano S. Santos, Mateus L. Nogueira, Felipe P. de Oliveira, Milena B. P. Soares, Aurilene G. Cajado, Roberto Cesar P. Lima Junior, Rosemayre Freire, Franciele B. F. Silva, Durcilene A. Silva, Fábio O. S. Ribeiro, Daniel P. Bezerra, Rosane B. Dias, José D. B. Marinho-Filho, Ana J. AraújoAbstract
Arabinogalactans are macromolecules with potential antitumor and antimetastatic effects, acting through modulation of the immune system, which makes them promising candidates for cancer immunotherapy. This study evaluated the immunomodulatory, antitumor, antimetastatic, and toxicological effects of an arabinogalactan isolated from Anadenanthera colubrina (RAG). RAG was structurally characterized by NMR, FTIR, zeta potential, and elemental analyses. Tumor and metastatic models were established in immunosuppressed mice transplanted with human colorectal cancer HCT-116 cells via subcutaneous and intravenous injections. After treatment, tumor growth, lung metastases, relative organ weight, histopathology, and immunofluorescence were evaluated. Structural characterization confirmed the presence of an arabinogalactan, with a protein content of 1.35% and a zeta potential of −29.47 mV. RAG significantly inhibited tumor growth by 63.5 ± 6.5% and 62.9 ± 8.3% at doses of 50 and 100 mg/kg/day, respectively, with areas of tumor necrosis observed. At the 100 mg/kg/day dose, no lung metastases were detected, whereas control and 50 mg/kg/day groups presented micrometastases and central necrosis. RAG also enhanced the antitumor immune response by increasing macrophage infiltration and promoting a pro-inflammatory macrophage-associated response, as indicated by increased expression of F4/80, TNF-α, and IL-12β, with no significant changes in IL-10. The expression of CD86 and CD206 showed no statistical difference, however, a trend toward increased CD86 and decreased CD206 was observed in treated groups. Regarding safety, no relevant histopathological alterations were observed at the 50 mg/kg/day dose, whereas the 100 mg/kg/day dose induced moderate vascular congestion and hepatic hemorrhagic infiltration. These findings suggest that RAG is a promising candidate for cancer immunotherapy, exerting antitumor and antimetastatic effects through activation of innate immunity.