Department of Microbiology, Immunology, and Pathology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC, 29209, USA.
Neurochem Res. 2020 Oct;45(10):2336-2351. doi: 10.1007/s11064-020-03093-0. Epub 2020 Jul 18.
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.
葫芦巴（Trigonella foenum-graecum）种子和野山药（Dioscorea villosa）根具有营养和药用特性，在传统医学中已被使用数百年，用于治疗各种疾病和炎症反应。薯蓣皂素是一种从葫芦巴和野山药中提取的天然甾体皂素，是治疗糖尿病、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，薯蓣皂素作为一种抗肿瘤剂，在抑制许多癌症（如结肠癌、白血病、乳腺癌和肝癌）的细胞增殖和诱导细胞凋亡方面具有有前景的效果。我们研究了不同浓度（5、10、15、20 和 25µM）薯蓣皂素对大鼠 C6 和人 T98G 神经胶质瘤细胞系增殖的影响。我们注意到薯蓣皂素对 C6 和 T98G 细胞系的生长均有很强的抑制作用。薯蓣皂素诱导神经胶质瘤细胞分化，表现为胶质纤维酸性蛋白（GFAP）分化标志物表达增加；并降低细胞去分化，表现为去分化标志物蛋白 Id2、N-Myc、端粒酶逆转录酶（TERT）和 Notch-1 的丰度降低。它还诱导 C6 和 T98G 细胞系凋亡，诱导凋亡涉及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，薯蓣皂素诱导的细胞迁移抑制与基质金属蛋白酶 2（MMP2）和 MMP9 表达降低有关；血管生成抑制，通过管形成试验确定，与血管内皮生长因子（VEGF）和成纤维细胞生长因子 2（FGF2）蛋白水平降低有关。总之，薯蓣皂素通过诱导分化和凋亡以及抑制迁移、侵袭和血管生成，对神经胶质瘤细胞显示出抗肿瘤作用。
