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Diosgenin as a Novel Alternative Therapy for Inhibition of Growth, Invasion, and Angiogenesis Abilities of Different Glioblastoma Cell Lines.
Neurochemical Research ( IF 3.7 ) Pub Date : 2020-07-18 , DOI: 10.1007/s11064-020-03093-0
Firas Khathayer 1 , Swapan K Ray 1
Affiliation  

Fenugreek (Trigonella foenum-graecum) seeds and roots of wild yam (Dioscorea villosa) possess nutritional and medicinal properties and have been used for centuries in traditional medicine to treat different diseases and inflammatory responses. Diosgenin is a natural steroidal sapogenin extracted from fenugreek and wild yam and it is one of the major bioactive compounds used in the treatment of diabetes, hypercholesterolemia, and inflammation. Recent studies have shown a promising effect of diosgenin as an anti-tumor agent for inhibition of cell proliferation and induction of apoptosis in many cancers such as colon cancer, leukemia, breast cancer, and liver cancer. We examined the effects of different concentrations (5, 10, 15, 20, and 25 µM) of diosgenin on proliferation of rat C6 and human T98G glioblastoma cell lines. We noticed that diosgenin had a high inhibitory effect on the growth of both C6 and T98G cell lines. Diosgenin induced the differentiation of glioblastoma cells, as determined by the increase in the expression of the differentiation marker glial fibrillary acidic protein (GFAP); and decreased the dedifferentiation of the cells, as shown by the decrease in the abundance of the dedifferentiation marker proteins Id2, N-Myc, telomerase reverse transcriptase (TERT), and Notch-1. It also induced apoptosis in C6 and T98G cell lines and the molecular mechanisms involved in the induction of apoptosis included increase in pro-apoptotic Bax protein and decrease in anti-apoptotic Bcl-2 protein. Further, the diosgenin-induced suppression of cell migration was correlated with the decrease in expression of matrix metalloproteinase 2 (MMP2) and MMP9; and the inhibition of angiogenesis, as determined by the tube formation assay, was correlated with a decrease in the protein levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2). In conclusion, diosgenin showed anti-tumor effects in glioblastoma cells by induction of differentiation and apoptosis and inhibition of migration, invasion, and angiogenesis.



中文翻译:

薯gen皂素是一种抑制不同胶质母细胞瘤细胞系生长,侵袭和血管生成能力的新型替代疗法。

胡芦巴(Trigonella foenum - graecum)种子和野山药根(Dioscorea villosa))具有营养和药用特性,并已在传统医学中使用了多个世纪,用于治疗各种疾病和炎症反应。薯gen皂甙元是从胡芦巴和野生山药中提取的天然甾体皂甙元,是用于治疗糖尿病,高胆固醇血症和炎症的主要生物活性化合物之一。最近的研究表明薯di皂苷元作为抗肿瘤剂在许多癌症如结肠癌,白血病,乳腺癌和肝癌中具有抑制细胞增殖和诱导细胞凋亡的作用。我们检查了不同浓度(5、10、15、20和25 µM)薯di皂苷元对大鼠C6和人T98G胶质母细胞瘤细胞系增殖的影响。我们注意到薯di皂苷元对C6和T98G细胞系的生长均具有高度抑制作用。薯gen皂甙元诱导了胶质母细胞瘤细胞的分化,这由分化标记物胶质纤维酸性蛋白(GFAP)表达的增加确定。并通过减少去分化标记蛋白Id2,N-Myc,端粒酶逆转录酶(TERT)和Notch-1的丰度来显示降低细胞的去分化能力。它还诱导了C6和T98G细胞系的凋亡,诱导凋亡的分子机制包括促凋亡Bax蛋白增加和抗凋亡Bcl-2蛋白减少。此外,薯os皂苷元诱导的细胞迁移抑制与基质金属蛋白酶2(MMP2)和MMP9的表达降低有关。和通过血管形成试验确定的对血管生成的抑制,与血管内皮生长因子(VEGF)和成纤维细胞生长因子2(FGF2)的蛋白质水平降低相关。总之,薯os皂苷元通过诱导分化和凋亡以及抑制迁移,侵袭和血管生成,在胶质母细胞瘤细胞中显示出抗肿瘤作用。

更新日期:2020-07-18
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