Boric Acid Induces Oxidative Stress-Associated Cytotoxicity and Modulates Wnt Signaling in MALME-3M Cells.

Melanoma is an aggressive malignancy with high metastatic potential and frequent treatment resistance. Boric acid (BA), a bioactive boron-derived compound, has shown anticancer activity in several tumor models, although its molecular effects in melanoma remain incompletely understood. This study investigated the antiproliferative effects of BA in MALME-3M metastatic melanoma cells, with emphasis on oxidative status, apoptosis-related markers, cell-cycle progression, migration-related features, and Wnt signaling-associated molecules. Cell viability and clonogenic potential were assessed using MTT and colony-formation assays. Apoptosis-related changes were evaluated by RT-qPCR and Annexin A5 (ANXA5) ELISA. Cell-cycle distribution was evaluated descriptively by flow cytometry. Wnt pathway-related molecules were examined by RT-qPCR and Western blotting, while oxidative status was evaluated using Total Oxidant Status (TOS), Total Antioxidant Status (TAS), and Oxidative Stress Index (OSI) measurements. BA reduced cell viability in a concentration- and time-dependent manner and markedly reduced clonogenic capacity. BA treatment was associated with increased TOS, decreased TAS, altered apoptosis-related gene expression, increased ANXA5 levels, and G0/G1 accumulation with reduced S-phase representation. BA treatment also showed a tendency toward reduced wound closure and altered MMP2 and TIMP1 expression. The molecular expression profile was consistent with reduced canonical Wnt/β-catenin signaling and modulation of non-canonical Wnt-related components. Overall, BA exerted antiproliferative effects in MALME-3M cells accompanied by oxidative stress-associated cytotoxicity and changes in apoptosis-, cell-cycle-, migration-, and Wnt signaling-related markers. These findings support further validation of BA in additional melanoma models.