TAGRA 2025

In recent years, the link between cancer pathogenesis and neurotransmitter systems has gained increasing attention, particularly the regulatory role of dopamine in tumor biology. Dopamine, a monoamine neurotransmitter, can enhance antitumor responses through dopamine receptors (DRs). The Caco-2 colorectal adenocarcinoma cell line serves as a suitable model for studying DR-mediated signaling and anticancer agents interacting with these pathways. Among therapeutic molecules, SN-38 (the active metabolite of irinotecan) exerts strong cytotoxicity via DNA topoisomerase I inhibition, while iron oxide nanoparticles (FeO NPs) exhibit anticancer activity through ROS generation, modulation of intracellular stress responses, and selective uptake by cancer cells. This study evaluated the anticancer effects of SN-38 and FeO NPs on Caco-2 cells and explored the potential involvement of dopaminergic signaling in these responses. Materials and Methods: Caco-2 cells were cultured under standard cell culture conditions. Once optimal conditions were achieved, the SN-38 anticancer agent encapsulated within nanoparticles was administered at defined doses (SN-38 10 nM + FeO 25 µg/mL and SN-38 10 nM + FeO 50 µg/mL). After 24 hours of treatment, cells and media were collected for analysis. Cell viability was assessed by MTT assay; oxidative stress parameters were evaluated using TAS and TOS assays; and the gene expression levels of dopamine receptor 1 and dopamine receptor 2 were examined. Results: The findings showed that the combined application of both molecules significantly reduced cell viability (approximately 25–40%) and disrupted oxidative stress balance to the detriment of tumor cells. The increase in TOS levels and decrease in TAS levels supported the conclusion that the treatment combinations enhanced pro-oxidant activity. Conclusion: This study demonstrates that the combination of SN-38 and iron oxide nanoparticles produces a pronounced anticancer effect in Caco-2 cells. The SN-38/FeO nanoparticle combination appears to be a promising therapeutic approach for colorectal cancer.