Laboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores-Zaragoza, Universidad Nacional Autónoma de México, Iztapalapa, México.
Laboratorio de Microscopía Electrónica, Depto. Biología Celular, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México, México.
Biol Cell. 2024 Mar;116(3):e2300052. doi: 10.1111/boc.202300052. Epub 2024 Feb 26.
Antiproliferative and apoptotic activities have been attributed to the phytosteroid diosgenin ((25R)-spirost-5-en-3β-ol; 1). It is known that combining glucose with two rhamnoses (the chacotrioside framework) linked to diosgenin increases its apoptotic activity. However, the effects of diosgenin glucosamine glycosides on different cancer cell types and cell death have not been entirely explored.
This study reports the antiproliferative, cytotoxic, and apoptotic activities of diosgenin and its glycosylated derivative ((25R)-spirost-5-en-3β-yl β-D-glucopyranoside; 2). It also explores the effects of two diosgenin glucosamine derivates, diosgenin 2-acetamido-2-deoxy-β-D-glucopyranoside (3), and diosgenin 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride (4), on different cancer cell lines. We found that all the compounds affected proliferative activity with minimal toxicity. In addition, all cancer cell lines showed morphological and biochemical characteristics corresponding to an apoptotic process. Apoptotic cell death was higher in all cell lines treated with compounds 2, 3 and 4 than in those treated with diosgenin. Moreover, compounds 3 and 4 induced apoptosis better than compounds 1 and 2. These results suggest that combining glucosamine with modified glucosamine attached to diosgenin has a greater apoptotic effect than diosgenin or its glycosylated derivative (compound 2). Furthermore, diosgenin and the abovementioned glycosides had a selective effect on tumour cells since the proliferative capacity of human lymphocytes, keratinocytes (HaCaT) and epithelial cells (CCD841) was not significantly affected.
Altogether, these results demonstrate that diosgenin glucosamine compounds exert an antiproliferative effect on cancer cell lines and induce apoptotic effects more efficiently than diosgenin alone without affecting non-tumour cells.
This study evidences the pro-apoptotic and selective activities of diosgenyl glucosamine compounds in cancer cell lines.
植物甾醇薯蓣皂素（(25R)-螺甾-5-烯-3β-醇；1）具有抗增殖和促凋亡活性。已知，将葡萄糖与连接在薯蓣皂素上的两个鼠李糖（沙壳三糖苷骨架）结合可以提高其促凋亡活性。然而，薯蓣皂素氨基葡萄糖糖苷对不同类型癌细胞和细胞死亡的影响尚未完全被探索。
本研究报告了薯蓣皂素及其糖苷化衍生物（(25R)-螺甾-5-烯-3β-基-β-D-吡喃葡萄糖苷；2）的抗增殖、细胞毒性和促凋亡活性。它还探索了两种薯蓣皂素氨基葡萄糖衍生物，薯蓣皂素 2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖苷（3）和薯蓣皂素 2-氨基-2-脱氧-β-D-吡喃葡萄糖苷盐酸盐（4）对不同癌细胞系的影响。我们发现，所有化合物均以最小的毒性影响增殖活性。此外，所有癌细胞系均表现出与凋亡过程相对应的形态学和生化特征。与用薯蓣皂素处理的细胞相比，用化合物 2、3 和 4 处理的所有癌细胞系的凋亡细胞死亡更高。此外，化合物 3 和 4 诱导凋亡的效果优于化合物 1 和 2。这些结果表明，将氨基葡萄糖与连接在薯蓣皂素上的修饰氨基葡萄糖结合使用比薯蓣皂素或其糖苷化衍生物（化合物 2）具有更强的促凋亡作用。此外，薯蓣皂素和上述糖苷对肿瘤细胞具有选择性作用，因为人淋巴细胞、角质形成细胞（HaCaT）和上皮细胞（CCD841）的增殖能力没有受到显著影响。
总之，这些结果表明，薯蓣皂素氨基葡萄糖化合物对癌细胞系具有抗增殖作用，并比单独使用薯蓣皂素更有效地诱导凋亡作用，而不影响非肿瘤细胞。
本研究证明了薯蓣皂素氨基葡萄糖化合物在癌细胞系中的促凋亡和选择性活性。
