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

Abstract

Anti-proliferative effects of halogenated boroxine – K2(B3O3F4OH) (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 in vitro as well as on the expression of cell death-related genes BCL-2, BECN1, DRAM1, and SQSTM1. 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 BCL-2 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 BCL-2 expression in normal (PBM) cells, probably by activating protective mechanisms against induced cytotoxicity. In addition, all but the lowest HB concentrations significantly upregulated SQSTM1 (P=0.001) in GR-M cells. Upregulated BECN1 expression suggests early activation of autophagy at the lowest HB concentration in SQSTM1 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.

Halogenated Boroxine K2[B3O3F4OH] Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line

“…Molecules 2024, 29, x FOR PEER REVIEW 3 of 15 cell line, HB significantly downregulates the relative expression of IGF-1, hTERT, and BCL-2 genes [24,30], suggesting its antitumor activity. At a physiological concentration of Ca 2+ , HB inhibits the growth of tumor cells without having such an effect on normal cells [31].…”

“…It acts as an inhibitor of horseradish peroxidase (HRP) [ 26 ], catalase [ 27 ], superoxide dismutase [ 28 ], and carbonic anhydrases [ 29 ]. In the GR-M cell line, HB significantly downregulates the relative expression of IGF-1 , hTERT , and BCL-2 genes [ 24 , 30 ], suggesting its antitumor activity. At a physiological concentration of Ca 2+ , HB inhibits the growth of tumor cells without having such an effect on normal cells [ 31 ].…”