Postgraduate Program in Biological Sciences: Biochemistry Toxicology, Biochemistry and Oxidative Stress Section of the Therapy Laboratory Cellular, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Postgraduate Program in Biological Sciences: Biochemistry Toxicological, Department of Chemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Mol Biol Rep. 2020 Jun;47(6):4393-4400. doi: 10.1007/s11033-020-05500-9. Epub 2020 May 14.
Glioblastoma multiforme (GM) is the most prevalent tumor among gliomas and presents the highest mortality rate among brain tumors. Berberine (BBR) is an alkaloid isoquinoline found in medicinal plants such as Coptis chinensis. Studies have been showed that BBR presents protective activity in mesenchymal cells and neurons, and antitumor properties in breast cancer and hepatocarcinoma. The aim of this study was to investigate the antitumor effects of BBR in GM U87MG cells, as well as to identify, whether such effects are mediated by oxidative stress and canonical apoptotic pathways. After treatment with several concentrations of BBR (10, 25, 100 and 250 µM) for 24, 48 and 72 h of exposure, BBR reduce cell viability of U87MG cells in a concentration- and time-dependent manner. Afterwards, it was observed that BBR, starting at a concentration of 25 µM of 24 h exposure, significantly suppressed proliferation and increased early apoptosis (53.5% ± 11.15 of annexin V propidium iodide cells) compared to untreated cells (7.5% ± 4.6). BBR-induced apoptosis was independent from AMPK activity and did not change total caspase-3 and p-p53 levels. Moreover, BBR (25 μM/24 h) increased oxidative stress in U87MG cells, evidenced by high levels of reactive oxygen species, thiobarbituric acid reactive substance and protein carbonylation. Considering the antitumor effects of BBR in U87MG cells, this compound may be a potential candidate for adjuvant GM treatment.
多形性胶质母细胞瘤（GBM）是神经胶质瘤中最常见的肿瘤，也是脑瘤中死亡率最高的肿瘤。小檗碱（BBR）是一种在黄连等药用植物中发现的异喹啉生物碱。研究表明，BBR 在间充质细胞和神经元中具有保护活性，并在乳腺癌和肝癌中具有抗肿瘤特性。本研究旨在探讨 BBR 对 GBM U87MG 细胞的抗肿瘤作用，并确定其是否通过氧化应激和经典凋亡途径发挥作用。用不同浓度的 BBR（10、25、100 和 250 μM）处理 U87MG 细胞 24、48 和 72 h 后，BBR 以浓度和时间依赖的方式降低 U87MG 细胞的活力。结果表明，BBR 从 25 μM 浓度和 24 h 暴露开始，与未处理细胞（7.5%±4.6）相比，显著抑制增殖并增加早期凋亡（53.5%±11.15%的 Annexin V 碘化丙啶细胞）。BBR 诱导的细胞凋亡不依赖于 AMPK 活性，也不改变总 caspase-3 和 p-p53 水平。此外，BBR（25 μM/24 h）增加了 U87MG 细胞中的氧化应激，这一点可以通过高水平的活性氧、硫代巴比妥酸反应性物质和蛋白质羰基化来证明。鉴于 BBR 对 U87MG 细胞的抗肿瘤作用，该化合物可能是辅助 GBM 治疗的潜在候选药物。
