Kumar Sunil, Gupta Aditi, Saini Reena Vohra, Kumar Amit, Dhar Kanaya Lal, Mahindroo Neeraj
School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Bajhol, Solan, Himachal Pradesh 173229, India.
School of Biotechnology, Shoolini University of Biotechnology and Management Sciences, Bajhol, Solan, Himachal Pradesh 173229, India.
Bioorg Med Chem. 2020 Jun 15;28(12):115552. doi: 10.1016/j.bmc.2020.115552. Epub 2020 May 11.
Immunomodulation activity-guided fractionation of ethanol extract of Brugmansia suaveolens leaves was carried out to isolate a novel compound SUPH036-022A (1) by co-culturing the test fraction/compound activated PBMC with MCF7 and A549 cancer cell lines. Assessment of immune markers in PBMC, and analysis of apoptosis markers and cell cycle was carried out for cancer cells. The structure of the isolated compound was elucidated by spectral analysis. Compound 1 enhanced the secretion of immune markers, IL-2 and IFN-γ, from PBMC. Further, compound 1 treated PBMC increased cell death in MCF7 and A549 cell lines and induced ROS production and mitochondrial membrane perturbation, leading to apoptosis. Flow cytometry analysis revealed; compound 1 stimulated PBMC to cause a five-fold increase in cell cycle perturbations in the sub-G1 stage of cancer cells as compared to the negative control. The compound, in the absence of PBMC, only had a weak cytotoxic activity against these cell lines. Thus, compound 1 is a novel lead for immunomodulation-mediated anticancer activity.
对光滑曼陀罗叶乙醇提取物进行免疫调节活性导向的分离,通过将测试级分/化合物激活的外周血单核细胞(PBMC)与MCF7和A549癌细胞系共培养,分离得到一种新型化合物SUPH036 - 022A(1)。对PBMC中的免疫标志物进行评估,并对癌细胞的凋亡标志物和细胞周期进行分析。通过光谱分析阐明了分离化合物的结构。化合物1增强了PBMC中免疫标志物IL - 2和IFN -γ的分泌。此外,用化合物1处理的PBMC增加了MCF7和A549细胞系中的细胞死亡,并诱导了活性氧(ROS)的产生和线粒体膜扰动,从而导致细胞凋亡。流式细胞术分析显示,与阴性对照相比,化合物1刺激PBMC导致癌细胞亚G1期的细胞周期扰动增加了五倍。在没有PBMC的情况下,该化合物对这些细胞系仅具有微弱的细胞毒性活性。因此,化合物1是免疫调节介导的抗癌活性的新型先导化合物。