Effects of boric acid on invasion, migration, proliferation, apoptosis and miRNAs in medullary thyroid cancer cells

Abstract

Abstract Background Medullary thyroid cancer (MTC) is an aggressive, chemoresistant form originating from the thyroid parafollicular C cells, has spurred interest in alternative treatments like boric acid, a boron-based compound has demonstrated anti-carcinogenic effects. Materials and Methods Cell viability were determined using 2,3-bis(2-methoxy-4 nitro-5- sulfophenyl- 2H-tetrazolium- 5-carboxanilide (XTT) assay.. Total RNA was isolated with Trizol reagent for gene and miRNA analysis via reverse transcription polymerase chain reaction (RT-PCR). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL) and comet assays evaluated boric acid's impact on apoptosis and genotoxicity, respectively. We also examined its influence on cell invasion, colony formation, and migration using matrigel- chamber, colony formation, and wound healing assays. Results 50% lethal dose (IC50) of boric acid was 35 µM at 48 hours. Real-time PCR showed changes at apoptosis-related genes, and miRNAs post-treatment. Significant increases in the expression of NOXA, apoptotic protease activating factor 1 (APAF-1), Bcl-2-associated X protein (Bax), caspase-3, and caspase-9, which are associated with apoptosis, were observed. Additionally, the expression of B-cell lymphoma 2 (bcl2), B- cell lymphoma‐ extra-large (bcl-xl), and microRNA-21 (miR-21), which are linked to the aggressiveness of MTC, was significantly reduced. The TUNEL assay revealed a 14% apoptosis rate, while assays showed a 30.8% decrease in cell invasion, a 67.9% decrease in colony formation, reduced cell migration, and increased DNA breaks post-treatment. Conclusions In conclusion, our findings suggest that boric acid may have potential as an anticancer agent in medullary thyroid cancer and other cancers with similar mechanisms.