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GB7 acetate, a galbulimima alkaloid from Galbulimima belgraveana, possesses anticancer effects in colorectal cancer cells
Journal of Pharmaceutical Analysis ( IF 8.8 ) Pub Date : 2021-06-27 , DOI: 10.1016/j.jpha.2021.06.007
Ziyin Li 1 , Lianzhi Mao 1 , Bin Yu 2 , Huahuan Liu 1 , Qiuyu Zhang 1 , Zhongbo Bian 1 , Xudong Zhang 1 , Wenzhen Liao 1 , Suxia Sun 1
Affiliation  

GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana. However, information regarding its structure, biological activities, and related mechanisms is not entirely available. A series of spectroscopic analyses, structural degradation, interconversion, and crystallography were performed to identify the structure of GB7 acetate. The MTT assay was applied to measure cell proliferation on human colorectal cancer HCT 116 cells. The expressions of the related proteins were measured by Western blotting. Transmission electron microscopy (TEM), acridine orange (AO) and monodansylcadaverine (MDC) staining were used to detect the presence of autophagic vesicles and autolysosomes. A transwell assay was performed to demonstrate metastatic capabilities. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) assays were performed to determine the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis activity of HCT 116 cells. The data showed that GB7 acetate suppressed the proliferation and colony-forming ability of HCT 116 cells. Pretreatment with GB7 acetate significantly induced the formation of autophagic vesicles and autolysosomes. GB7 acetate upregulated the expressions of LC3 and Thr172 phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase α (p-AMPKα), which are key elements of autophagy. In addition, GB7 acetate suppressed the metastatic capabilities of HCT 116 cells. Additionally, the production of matrix metallo-proteinase-2 (MMP-2) and MMP-9 was reduced, whereas the expression of E-cadherin (E-cad) was upregulated. Furthermore, GB7 acetate significantly reduced mitochondrial OXPHOS and glycolysis. In conclusion, the structure of the novel Galbulimima alkaloid GB7 acetate was identified. GB7 acetate was shown to have anti-proliferative, pro-autophagic, anti-metastatic, and anti-metabolite capabilities in HCT 116 cells. This study might provide new insights into cancer treatment efficacy and cancer chemoprevention.



中文翻译:

GB7 醋酸盐是一种来自 Galbulimima belgraveana 的 galbulimima 生物碱,对结直肠癌细胞具有抗癌作用

GB7 醋酸盐是一种从Galbulimima belgraveana获得的galbulimima生物碱. 然而,关于其结构、生物活性和相关机制的信息并不完全可用。进行了一系列光谱分析、结构降解、相互转化和结晶学以确定 GB7 醋酸盐的结构。MTT 测定法用于测量人结肠直肠癌 HCT 116 细胞的细胞增殖。Western blotting检测相关蛋白的表达。透射电子显微镜 (TEM)、吖啶橙 (AO) 和单丹磺酰尸胺 (MDC) 染色用于检测自噬囊泡和自溶酶体的存在。进行了 transwell 测定以证明转移能力。进行耗氧率 (OCR) 和细胞外酸化率 (ECAR) 测定以确定 HCT 116 细胞的线粒体氧化磷酸化 (OXPHOS) 和糖酵解活性。数据显示GB7醋酸盐抑制HCT 116细胞的增殖和集落形成能力。用GB7醋酸盐预处理显着诱导自噬囊泡和自溶酶体的形成。GB7 醋酸盐上调 LC3 和 Thr172 磷酸化腺苷 5'-一磷酸 (AMP) 活化蛋白激酶 α (p-AMPKα) 的表达,它们是自噬的关键要素。此外,GB7 醋酸盐抑制 HCT 116 细胞的转移能力。此外,基质金属蛋白酶 2 (MMP-2) 和 MMP-9 的产生减少,而 E-cadherin (E-cad) 的表达上调。此外,GB7 醋酸盐显着降低线粒体 OXPHOS 和糖酵解。总之,小说的结构鉴定了 Galbulimima生物碱 GB7 醋酸盐。GB7 醋酸盐在 HCT 116 细胞中被证明具有抗增殖、促自噬、抗转移和抗代谢物的能力。这项研究可能为癌症治疗效果和癌症化学预防提供新的见解。

更新日期:2021-06-27
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