Yeditepe University, Department of Genetics and Bioengineering, Faculty of Engineering, Istanbul, Turkey.
J Trace Elem Med Biol. 2022 Mar;70:126923. doi: 10.1016/j.jtemb.2022.126923. Epub 2022 Jan 4.
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.
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.
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.
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.
硼具有抗癌活性。尽管已经发现许多硼衍生物，如硼酸（BA），具有抗癌作用，但仍有许多硼衍生物的抗癌作用尚未被发现。其中一些包括五硼酸钠五水合物（NaB），其抗癌作用的研究有限，以及过硼酸钠四水合物（SPT），其抗癌作用尚未发现。本研究旨在探讨硼酸（BA）、五硼酸钠五水合物（NaB）和过硼酸钠四水合物（SPT）对体外小细胞肺癌（SCLC）细胞系 DMS-114 细胞的抗癌作用。
采用 MTS 法检测 BA、NaB 和 SPT 的 EC50 浓度及其对细胞存活的影响。集落形成单位（CFU）测定法评估它们对细胞集落形成能力的影响。通过 Annexin-V 测定法确定它们对细胞凋亡的影响。进行细胞周期分析以了解细胞周期在哪个阶段被阻滞。实时 PCR（RT-PCR）用于评估凋亡、抗凋亡和肿瘤抑制基因的 mRNA 水平。Western blot 用于测定 p53 和 Caspase 3 的蛋白水平。
DMS-114 细胞在 72 小时的 BA、NaB 和 SPT 处理后，细胞存活率下降，DMS-114 和 MRC-5 细胞在 BA 处理中的 EC50 浓度相差 5.5 倍，NaB 处理相差 5.2 倍，SPT 处理相差 10 倍。在 BA、NaB 和 SPT 处理组中，集落单位数分别从 350 减少到 128、从 320 减少到 95 和从 430 减少到 96。在 BA、NaB 和 SPT 处理 72 小时后，细胞凋亡分别增加了 10%、19%和 42%。BA、NaB 和 SPT 处理 72 小时后，一些促凋亡和肿瘤抑制基因上调，一些抗凋亡基因下调。BA 和 NaB 处理组在 G2/M 期，SPT 处理组在 Sub-G1 期检测到细胞周期阻滞。BA、NaB 和 SPT 处理 72 小时后，P53 和 Caspase 3 的蛋白水平增加。
BA、NaB 和 SPT 在不损伤 MRC-5 细胞的情况下对 DMS-114 细胞系表现出抗癌活性，部分分子机制涉及细胞凋亡和细胞周期阻滞。
