Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan.
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
Int J Mol Sci. 2021 Sep 28;22(19):10453. doi: 10.3390/ijms221910453.
Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood-brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.
地奥司明是一种天然黄酮糖苷，通过类似黄烷酮糖苷橙皮苷的脱氢获得，存在于许多柑橘类水果中。多形性胶质母细胞瘤（GBM）是最恶性的原发性脑肿瘤；在标准治疗后，GBM 患者的平均生存时间不到 18 个月。本研究表明，能够穿过血脑屏障的地奥司明在体外和体内均能抑制 GBM 细胞的生长。地奥司明还通过抑制上皮-间充质转化来阻止 GBM8401 和 LN229 GBM 细胞的迁移和侵袭，这表现为 E-钙黏蛋白表达增加和 Snail 和 Twist 表达减少。地奥司明还抑制自噬流，表现为 LC3-II 和 p62 的表达增加，并诱导细胞周期停滞在 G1 期。重要的是，地奥司明对对照 SVG-p12 星形胶质细胞没有严重的细胞毒性作用，尽管它在高浓度时确实降低了星形胶质细胞的活力。这些发现为开发治疗 GBM 的新疗法提供了潜在的有益支持。
