New findings about halogenated boroxine cytotoxicity and deregulation of cell death-related genes in GR-M melanoma cells.

Anti-proliferative effects of halogenated boroxine - K(BOFOH) (HB) - have been confirmed in multiple cancer cell lines, including melanoma, but the exact mechanism of action is still unknown. This study aimed to determine its cytotoxic effects on human Caucasian melanoma (GR-M) cell growth as well as on the expression of cell death-related genes , and . GR-M and peripheral blood mononuclear (PBM) cells were treated with different HB concentrations and their growth inhibition and relative gene expression profiles were determined using the Alamar blue assay and real-time PCR. HB significantly inhibited cell growth of both GR-M and PBM cells but was even more effective in GR-M melanoma cells, as significant inhibition occurred at a lower HB concentration of 0.2 mg/mL. GR-M expression was significantly downregulated (P=0.001) at HB concentration of 0.4 mg/mL, which suggests that HB is a potent tumour growth inhibitor. At the same time, it upregulated expression in normal (PBM) cells, probably by activating protective mechanisms against induced cytotoxicity. In addition, all but the lowest HB concentrations significantly upregulated (P=0.001) in GR-M cells. Upregulated expression suggests early activation of autophagy at the lowest HB concentration in cells and at all HB concentrations in PBM cells. Our findings clearly show HB-associated cell death and, along with previous cytotoxicity studies, reveal its promising anti-tumour potential.