Chalcona hidroxilada inibe a migração e a adesão celular em modelo in vitro de carcinoma espinocelular oral

Abstract

Oral squamous cell carcinoma (OSCC) is the most prevalent type of head and neck cancer, characterized by highly invasive behavior and frequently associated with the development of metastases, the main cause of mortality among patients. Conventional chemotherapy, widely employed in the treatment of this neoplasm, faces significant limitations due to its severe adverse effects and low selectivity for tumor cells. These factors compromise patients' quality of life and reduce therapeutic efficacy. In this context, medicinal chemistry has emerged as a promising approach in the search for new molecules capable of halting tumor progression. Among the compounds investigated, chalcones have attracted attention due to their broad biological potential, particularly their antiproliferative and antimetastatic activities. Accordingly, the present study aimed to evaluate the effects of a synthetic hydroxylated

chalcone containing a chlorine substituent at the para-position of the B-ring, referred to as HC- A3, on key steps of the metastatic process in oral squamous cell carcinoma, using an in vitro

model. Initially, the cytotoxic profile of HC-A3 was assessed against the HSC-3 cell line. Using the MTT assay after 24, 48, and 72 hours of treatment, HC-A3 demonstrated a time-dependent cytotoxic effect, with IC50 values ranging from entre 45.4 to 8.3 μM. Based on the IC50 values obtained after 72 hours of treatment, sub-cytotoxic concentrations of 0.25, 0.5, and 1.0 μM were selected for subsequent experiments and confirmed through trypan blue exclusion assay and morphological analysis. In the clonogenic assay, HC-A3 did not impair the proliferative capacity of the cells, as it did not inhibit colony formation. However, at the tested concentrations, HC-A3 significantly inhibited cell migration after 24 and 48 hours of exposure compared to the negative control. Furthermore, the compound markedly reduced cell adhesion to fibronectin. Based on these findings, HC-A3 demonstrated both cytotoxic potential and the ability to inhibit critical steps of the metastatic process. Nevertheless, further studies are required to elucidate the molecular mechanisms underlying their effects on migration and adhesion events associated with metastasis.