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

• Published in: Arhiv za higijenu rada i toksikologiju Vol. 74; no. 1; pp. 16 - 21
• Main Authors: Elez-Burnjaković, Nikolina, Pojskić, Lejla, Haverić, Anja, Lojo-Kadrić, Naida, Omanović, Maida Hadžić, Ramić, Jasmin, Smajlović, Ajla, Maksimović, Milka, Haverić, Sanin
• Format: Journal Article
• Language: English
• Published: Croatia Sciendo 01-03-2023; Institute for Medical Research and Occupational Health
• Subjects: anti-proliferative effect; antiproliferativni učinak; Apoptosis; Autophagy; bcl-2; Bcl-2 protein; becn1, dram1; Blood; Cell Death; Cell growth; Cell Line, Tumor; Cytotoxicity; Deregulation; Fluorometers; Gene expression; Genes; human Caucasian melanoma; Humans; Immune checkpoint inhibitors; Immunosuppressive agents; Leukocytes, Mononuclear - pathology; ljudski kavkaski melanom; Medical prognosis; Melanocytes; Melanoma; Melanoma - genetics; Melanoma - pathology; mononuklearne stanice periferne krvi; Mortality; Mutation; Original; Peripheral blood; peripheral blood mononuclear cell; Proteins; Proto-Oncogene Proteins c-bcl-2 - pharmacology; Qubits (quantum computing); Ribonucleic acid; RNA; Sequestosome-1 Protein; Skin cancer; sqstm1; Toxicity; Variance analysis; White people; St Louis Missouri; United Kingdom > UK; United States > US; Germany; anti-proliferative effect; BCL-2; antiproliferativni učinak; human Caucasian melanoma; ljudski kavkaski melanom; SQSTM1; mononuklearne stanice periferne krvi; BECN1, DRAM1; peripheral blood mononuclear cell
• ISSN: 1848-6312; 0004-1254; 1848-6312
• DOI: 10.2478/aiht-2023-74-3702

Anti-proliferative effects of halogenated boroxine – K
(B
OH) (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.