THERAPEUTIC POTENTIAL OF ARSENIUM TRIOXIDE IN METASTATIC LINE OF ORAL SCAMOCELLULAR CARCINOMA
Oral Cancer; Hedgehog Proteins; Drug Repurposing; Arsenic Trioxide.
ABSTRACT
INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) is the most common histological type of cancer in the oral cavity. Despite the impacts on the patients survival, only a few therapeutic advances have been observed, especially with regard to chemotherapy. So, pharmacological strategies to block signaling pathways related to embryonic development, such as downstream inhibition of the Hedgehog pathway, has stood out as a promising field and, therefore, the use of repositioned drugs, such as Arsenic Trioxide (ATO), represents a possible strategy for the treatment of this tumor. AIM: The aim of this study was to evaluate the therapeutic potential of Arsenic Trioxide (ATO) through the pharmacological inhibition of the HH pathway in a metastatic OSCC cell (HSC3). MATERIALS AND METHODS:
Alamar Blue assay was used to assess citotoxicity of different tumor and non-tumor cells. Initially, the effects of ATO on cell viability were evaluated using the Trypan Blue assay, at different incubation times. Furthermore, the activity of this drug on the cell cycle, cell death, and morphological changes at different times of incubation were evaluated by flow cytometry. Western Blot (WB) and Immunofluorescence (IF) assays were performed to evaluate the expression of HH pathways components and qPCR reactions using TaqMan Gene Expression
Assays ™. RESULTS: Alamar Blue assay showed greater sensitivity to treatment in HSC3 cells compared to others cells evaluated. Here, ATO was able to reduce components of the HH pathway and its target genes after 24h of treatment, indicating anti-HH activity. Moreover, cell cycle and death assays showed significant increase in nuclear fragmentation in the sub-G1 phase and cell death by apoptosis, and changes in cell morphology. CONCLUSIONS: ATO showed promising cytotoxic activity in a metastatic OSCC cell, being able to reduce the activity of the HH pathway in this tumor.