Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, 110 Bertelsmeyer Hall, 1101 N. State Street, Rolla, MO, 65409-1230, USA.
Sci Rep. 2021 Jan 14;11(1):1298. doi: 10.1038/s41598-020-80484-x.
Monogalactosyldiacylglycerol (MGDG) is the most abundant type of glycoglycerolipid found in the plant cell membrane and mostly in the chloroplast thylakoid membrane. The amphiphilic nature of MGDG is attractive in pharmaceutical fields for interaction with other biological molecules and hence exerting therapeutic anti-cancer, anti-viral, and anti-inflammatory activities. In this study, we investigated the therapeutic efficacy of cyanobacteria derived MGDG to inhibit breast cancer cell growth. MGDG was extracted from a cyanobacteria Synechocystis sp. PCC 6803 followed by a subsequent fractionation by column chromatographic technique. The purity and molecular structure of MGDG were analyzed by nuclear magnetic resonance (NMR) spectroscopy analysis. The presence of MGDG in the extracted fraction was further confirmed and quantified by high-performance liquid chromatography (HPLC). The anti-proliferation activity of the extracted MGDG molecule was tested against BT-474 and MDA-MB-231 breast cancer cell lines. The in vitro study showed that MGDG extracted from Synechocystis sp. PCC 6803 induced apoptosis in (70 ± 8) % of BT-474 (p < 0.001) and (58 ± 5) % of MDA-MB-231 cells (p < 0.001) using ~ 60 and 200 ng/ml of concentrations, respectively. The half-maximal inhibitory concentration, IC of MGDG extracted from Synechocystis sp. PCC 6803 were (27.2 ± 7.6) and (150 ± 70) ng/ml in BT-474 and MDA-MB-231 cell lines, respectively. Quantification of caspase-3/7 activity using flow cytometry showed (3.0 ± 0.4) and (2.1 ± 0.04)-fold (p < 0.001) higher protein expressions in the MGDG treated BT-474 and MDA-MB-231 cells, respectively than untreated controls conferring to the caspase-dependent apoptosis. The MGDG did not show any significant cytotoxic side effects in human dermal fibroblasts cells. A commercially available MGDG control did not induce any apoptotic cell death in cancer cells substantiating the potential of the MGDG extracted from Synechocystis sp. PCC 6803 for the treatment of breast cancer cells through the apoptosis-mediated pathway.
单半乳糖二酰基甘油 (MGDG) 是植物细胞膜中最丰富的糖脂类型，主要存在于叶绿体类囊体膜中。MGDG 的两亲性在制药领域具有吸引力，可与其他生物分子相互作用，从而发挥治疗癌症、抗病毒和抗炎的活性。在这项研究中，我们研究了源自蓝藻的 MGDG 抑制乳腺癌细胞生长的治疗功效。从蓝藻集胞藻 PCC 6803 中提取 MGDG 后，通过柱层析技术进行后续分离。通过核磁共振 (NMR) 光谱分析对 MGDG 的纯度和分子结构进行分析。通过高效液相色谱 (HPLC) 进一步确认和定量提取物中 MGDG 的存在。测试了从集胞藻 PCC 6803 中提取的 MGDG 分子对 BT-474 和 MDA-MB-231 乳腺癌细胞系的抗增殖活性。体外研究表明，从集胞藻 PCC 6803 中提取的 MGDG 在 60 和 200 ng/ml 的浓度下分别诱导 BT-474（p < 0.001）和 MDA-MB-231 细胞（p < 0.001）中的凋亡分别为（70 ± 8）%和（58 ± 5）%。集胞藻 PCC 6803 中提取的 MGDG 的半最大抑制浓度 IC 分别为 BT-474 细胞和 MDA-MB-231 细胞中的（27.2 ± 7.6）和（150 ± 70）ng/ml。使用流式细胞术定量检测 caspase-3/7 活性显示，MGDG 处理的 BT-474 和 MDA-MB-231 细胞中的蛋白表达分别比未处理对照高 3.0 ± 0.4 倍和 2.1 ± 0.04 倍（p < 0.001），表明这两种细胞均通过 caspase 依赖性凋亡。MGDG 对人真皮成纤维细胞没有显示出任何显著的细胞毒性副作用。商业上可获得的 MGDG 对照物未在癌细胞中诱导任何凋亡性细胞死亡，这证实了从集胞藻 PCC 6803 中提取的 MGDG 通过凋亡介导的途径用于治疗乳腺癌细胞的潜力。
