Chalcona Do Tipo Terpenóide Inibe Etapas-Chave Da Progressão Metastática In Vitro Em Células De Adenocarcinoma Colorretal

Abstract

Colorectal cancer (CRC) is among the most prevalent types of neoplasms worldwide and presents an unfavorable prognosis, mainly due to its high rate of metastasis, the leading cause of morbidity and mortality among patients. In this context, there is increasing interest in identifying new molecules capable of interfering with tumor cell dissemination. Within this framework, the synthesis of compounds based on natural products has become a strategic approach, allowing for the rational modification of bioactive structures to enhance their therapeutic effects and expand their pharmacological applicability. Chalcones and ionones have been highlighted for presenting several biological properties, including anticancer activity. Based on this perspective, the present study aimed to investigate the cytotoxic, antimigratory, and anti-adhesive effects of a terpenoid-like chalcone (BR4Cl), resulting from the structural combination of chalcone and ionone, in human colorectal adenocarcinoma cells (SW-480). Initially, the cytotoxic activity of BR4Cl was evaluated using the MTT assay, revealing IC50 values of 12.44 μM, 4.62 μM, and 3.64 μM after 24, 48, and 72 hours of treatment, respectively. Based on the 24-hour cell viability curve, subcytotoxic concentrations of 0.05 μM and 0.10 μM were established for cell adhesion and migration assays. Cell viability at these concentrations was confirmed by Trypan blue exclusion and morphological analysis using fast panoptic staining, with no significant alterations observed after 24 hours of exposure. In the clonogenic assay, BR4Cl did not significantly reduce the number or area of the colonies formed. On the other hand, the cell migration assay demonstrated that BR4Cl, at the tested concentrations, significantly inhibited the migration of SW-480 cells after 24 and 48 hours of treatment. Additionally, the cell adhesion assay indicated that BR4Cl significantly reduced cell adhesion to fibronectin, with inhibitions of 32.68% and 44.16% for 0.05 μM and 0.10 μM, respectively, after 24 hours of pretreatment. Taken together, these findings indicate that BR4Cl exhibits cytotoxic potential against CRC and is capable of interfering with critical steps in metastatic progression, such as cell migration and adhesion, in vitro. However, further studies are needed to elucidate the molecular mechanisms underlying these effects and to advance the evaluation of its therapeutic potential.