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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Erkmen T., Serdar B. S., Ateş H., Korkmaz M., Koçtürk A. S.

Biological trace element research, vol.200, no.4, pp.1608-1616, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 200 Issue: 4
  • Publication Date: 2022
  • Doi Number: 10.1007/s12011-021-02802-2
  • Journal Name: Biological trace element research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Page Numbers: pp.1608-1616
  • Keywords: Acute myeloid leukemia, Apoptosis, Borax pentahydrate, Disodium pentaborate decahydrate, BORIC-ACID, PROTEASOME INHIBITORS, TOPICAL TREATMENT, MULTIPLE-MYELOMA, BORON-COMPOUNDS, 20S PROTEASOME, INDUCED DEATH, BORTEZOMIB, POTENT, DERIVATIVES
  • Dokuz Eylül University Affiliated: Yes

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.