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Archives of Industrial Hygiene and Toxicology, Vol. 74 No. 1, 2023.

Original scientific paper

https://doi.org/10.2478/aiht-2023-74-3702

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

Nikolina Elez-Burnjaković orcid id orcid.org/0000-0002-1317-8399 ; University of East Sarajevo, Faculty of Medicine Foča, Department of Cell Biology and Human Genetics, Foča, Bosnia and Herzegovina
Lejla Pojskić orcid id orcid.org/0000-0003-2260-318X ; University of Sarajevo, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina
Anja Haverić orcid id orcid.org/0000-0002-2398-3535 ; University of Sarajevo, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina
Naida Lojo-Kadrić orcid id orcid.org/0000-0002-0534-1336 ; University of Sarajevo, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina
Maida Hadžić Omanović orcid id orcid.org/0000-0001-5336-421X ; University of Sarajevo, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina
Jasmin Ramić orcid id orcid.org/0000-0001-6673-1584 ; University of Sarajevo, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina
Ajla Smajlović ; University of Sarajevo, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina
Milka Maksimović orcid id orcid.org/0000-0001-7008-4500 ; University of Sarajevo, Faculty of Science, Sarajevo, Bosnia and Herzegovina
Sanin Haverić ; University of Sarajevo, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina

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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.

Keywords

anti-proliferative effect; BCL-2; BECN1, DRAM1; human Caucasian melanoma; peripheral blood mononuclear cell; SQSTM1

Hrčak ID:

296528

URI

https://hrcak.srce.hr/296528

Publication date:

28.3.2023.

Article data in other languages: croatian

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