College of Light Industry and Food Sciences, South China University of Technology, 381 Wushan Road, Guangzhou, 510640, China.
Amino Acids. 2011 Oct;41(4):923-32. doi: 10.1007/s00726-010-0791-0. Epub 2010 Nov 11.
Lung cancer is still difficult to treat by current chemotherapeutic procedures. We recently found that MVL, an anti-HIV lectin from blue-green algae Microcystis viridis, also has antitumor activity. The objective of this study was to investigate apoptosis-inducing activity of recombinant MVL (R-MVL) and proteomic changes in A549 cells, and to identify the molecular pathways responsible for the anti-cancer action of R-MVL. We found that R-MVL induces A549 cells apoptosis in a dose-dependent manner by using MTT assay, fluorescent microscope (FM) and flow cytometry (FCM), and the IC50 was calculated to be 24.12 μg/ml. Subsequently, 7 altered proteins in R-MVL-treated A549 cells were identified, including upregulated aldehyde dehydrogenase 1 and β-actin, and five downregulated proteins: heat shock protein 90, heat shock 60, plastin 3, tropomyosin 3, and β-tubulin. Further bioinformatics analysis predicted the potential pathways for R-MVL to induce apoptosis of A549 cells. In conclusion, this is the first report to investigate anti-cancer activity of R-MVL and its mechanism of action by proteomics analysis. Our observations provide potential therapeutic targets for lung cancer inhibitor intervention and implicated the development of novel anti-cancer therapeutic strategies.
目前的化疗程序仍然难以治疗肺癌。我们最近发现,来自蓝绿藻微囊藻的抗 HIV 凝集素 MVL 也具有抗肿瘤活性。本研究的目的是研究重组 MVL(R-MVL)诱导 A549 细胞凋亡的活性和蛋白质组变化,并确定 R-MVL 抗癌作用的分子途径。我们发现 R-MVL 通过 MTT 测定、荧光显微镜(FM)和流式细胞术(FCM)以剂量依赖的方式诱导 A549 细胞凋亡,IC50 计算为 24.12μg/ml。随后,在 R-MVL 处理的 A549 细胞中鉴定出 7 种改变的蛋白质,包括上调的醛脱氢酶 1 和 β-肌动蛋白,以及 5 种下调的蛋白质:热休克蛋白 90、热休克 60、肌动蛋白结合蛋白 3、原肌球蛋白 3 和β-微管蛋白。进一步的生物信息学分析预测了 R-MVL 诱导 A549 细胞凋亡的潜在途径。总之,这是首次通过蛋白质组学分析研究 R-MVL 的抗癌活性及其作用机制。我们的观察结果为肺癌抑制剂干预提供了潜在的治疗靶点,并暗示了新的抗癌治疗策略的发展。