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Published on: December 1, 2016
Anti-cancer effect of boron derivatives on small-cell lung cancer
Emre Cebeci1, Büşra Yüksel1, Fikrettin Şahin1
1Yeditepe University, Department of Genetics and Bioengineering, Faculty of Engineering, Istanbul, Turkey.
Background:
Anti-cancer activity of boron has been reported. Although many boron derivatives such as boric acid (BA) have been discovered to have anticancer effects, there are many boron derivatives whose anticancer effects have not yet been discovered. Some of these include sodium pentaborate pentahydrate (NaB), which has had limited research on its anticancer effects, and sodium perborate tetrahydrate (SPT), whose anticancer effect has yet to be discovered. The aim of this study was to investigate the anti-cancer effects of boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) against small-cell lung cancer (SCLC) cell line DMS-114 cells in vitro.
Methods:
EC50 concentrations and effects of BA, NaB, and SPT on cell survival were detected with an MTS assay. The colony-forming unit (CFU) assay was used to assess their effects on cell colony formation capability. Their effects on apoptosis were determined by an Annexin-V assay. A cell cycle analysis was performed to understand at what phase the cell cycle is arrested. Real-Time PCR (RT-PCR) was used to evaluate the mRNA levels of apoptotic, anti-apoptotic, and tumor suppressor genes. Western blotting was used to determine the protein levels of p53 and Caspase 3.
Results:
The survival rates of DMS-114 cells decreased with BA, NaB and SPT after 72 h of treatment and the EC50 concentrations of DMS-114 and MRC-5 cells differed 5.5-fold in BA treatment, 5,2-fold in NaB treatment and 10-fold in SPT treatment. Colony unit numbers were decreased from 350 to 128, from 320 to 95, and from 430 to 96 in the BA, NaB, and SPT treatment groups, respectively. The apoptosis increased by 10, 19, and 42 percent after treatment with BA, NaB, and SPT for 72 h, respectively. Following 72 h of treatment with BA, NaB, and SPT, some pro-apoptotic and tumor suppressor genes were upregulated and some anti-apoptotic genes were downregulated. Cell cycle arrests were detected at the G2/M phase in the BA, and NaB treatment groups and at the Sub-G1 phase in the SPT treatment group. The protein levels of P53 and Caspase 3 increased with BA, NaB and SPT treatment for 72 h.
Conclusions:
BA, NaB and SPT show anti-cancer activity in the DMS-114 cell line without damaging MRC-5 cells, and some of the molecular mechanisms are involved in apoptosis and cell cycle arrest.
Insights
Boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) demonstrated anti-cancer effects against small-cell lung cancer cells. These boron compounds induced apoptosis and cell cycle arrest, showing potential for cancer treatment.
Area of Science:
- Boron chemistry and its application in oncology.
- In vitro cancer cell line studies.
- Molecular mechanisms of anti-cancer drug action.
Background:
- Boron compounds, including boric acid (BA), exhibit known anti-cancer properties.
- Limited research exists on the anti-cancer effects of sodium pentaborate pentahydrate (NaB) and sodium perborate tetrahydrate (SPT).
- The anti-cancer potential of various boron derivatives remains largely unexplored.
Purpose of the Study:
- To investigate the in vitro anti-cancer effects of boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT).
- To evaluate these effects specifically against the small-cell lung cancer (SCLC) DMS-114 cell line.
- To explore the underlying molecular mechanisms of action.
Main Methods:
- Cell viability assessed using MTS assay to determine EC50 concentrations.
- Colony-forming unit (CFU) assay to evaluate effects on cell proliferation.
- Annexin-V assay for apoptosis detection, cell cycle analysis, RT-PCR for gene expression, and Western blotting for protein levels (p53, Caspase 3).
Main Results:
- BA, NaB, and SPT significantly reduced DMS-114 cell survival and colony formation.
- Apoptosis was increased by 10% (BA), 19% (NaB), and 42% (SPT) after 72h treatment.
- Treatment led to cell cycle arrest (G2/M for BA/NaB, Sub-G1 for SPT) and increased p53 and Caspase 3 protein levels.
Conclusions:
- Boric acid, sodium pentaborate pentahydrate, and sodium perborate tetrahydrate exhibit significant anti-cancer activity against the DMS-114 cell line.
- These boron compounds demonstrate selectivity, with minimal impact on non-cancerous MRC-5 cells.
- The anti-cancer effects are mediated through apoptosis induction and cell cycle arrest.
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