Borax Pentahydrate and Disodium Pentaborate Decahydrate Are Candidates as Anti-leukemic Drug Components by Inducing Apoptosis and Changing Bax/Bcl-2 Ratio in HL-60 Cell Line
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2022
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Abstract
Acute myeloid leukemia (AML) is the most common form of acute leukemia and has the lowest 5-year survival rates. Current treatment strategies do not meet the expectations also. Therefore, there is a need to improve therapeutic approaches still. Boron, which is a natural trace element in human diet, is gaining attention with its important roles in cellular processes for the development of new anti-cancer drug candidates. For instance, bortezomib, a dipeptidyl boronic acid, has encouraging results in the treatment of multiple myeloma and mantle cell lymphoma. However, severe toxic effects and resistance development are the limitations to its application for AML treatment. Hence, the development of alternative boron-derived anti-AML agents is unmet need. Therefore, we aimed to evaluate anti-leukemic effect of two promising boron compounds, borax pentahydrate (BP) and disodium pentaborate decahydrate (DPD), and comparison of each other in terms of the capacity to trigger apoptosis on acute promyelocytic leukemia cells (HL-60). Cell viability was assessed by MTT assay. Apoptotic effects of the boron compounds on HL-60 cells were evaluated by annexin V/propidium iodide dyes and caspase 3/7 activity assay by flow cytometry. In addition, Bax/Bcl-2 and cleaved PARP levels were detected by western blotting. Although BP showed greater apoptosis-inducing capacity, we observed that both DPD (6 mM) and BP (24 mM) treatment showed anti-leukemic effect by triggering apoptotic pathway through increasing Bax/Bcl-2 ratio for the first time. Our study suggests that BP and DPD are the promising candidates for anti-AML drug development research, which may be confirmed by further wide-spectrum studies. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Adult , Apoptosis , bcl-2-Associated X Protein , Borates , HL-60 Cells , Humans , Pharmaceutical Preparations , Proto-Oncogene Proteins c-bcl-2 , antineoplastic agent , borax pentahydrate , caspase 3 , caspase 7 , disodium pentaborate decahydrate , lipocortin 5 , protein Bax , protein bcl 2 , unclassified drug , borate sodium , boric acid , drug , protein Bax , protein bcl 2 , sodium pentaborate , antineoplastic activity , apoptosis , Article , enzyme activity , flow cytometry , HL-60 cell line , human , IC50 , MTT assay , Western blotting , adult , apoptosis , HL-60 cell line , metabolism