Diosmin induces caspase-dependent apoptosis in human glioblastoma cells

Abstract: Diosmin is a flavone glycoside clinically used as the main component of Daflon for the treatment of venous diseases. Several studies demonstrated that this natural compound can induce apoptosis in different tumors. However, isolated diosmin has not been studied regarding its effects on glioblastoma so far. Since glioblastoma is a highly lethal and fast-growing brain tumor, new therapeutic strategies are urgently needed. Herein, we evaluated the role of this flavonoid against glioblastoma cells using in vitro assays. Diosmin significantly reduced the viability of GBM95, GBM02, and U87MG glioblastoma cells, but not of healthy human astrocytes, as verified by MTT assay. Vimentin immunostaining showed that diosmin induced morphological changes in GBM95 and GBM02 cells, making them smaller and more polygonal. Diosmin did not inhibit GBM95 and GBM02 cell proliferation, but it caused DNA fragmentation, as verified by the TUNEL assay, and increased cleaved caspase-3 expression in these cells. In summary, diosmin is able to induce caspase-dependent apoptosis specifically in tumor cells and, therefore, could be considered a promising therapeutic compound against glioblastoma.

摘要：地奥司明（Diosmin）是一种黄酮苷类化合物，临床作为静脉疾病治疗药物Daflon的核心成分应用。多项研究证实，该天然化合物可诱导多种肿瘤细胞发生凋亡，但截至目前，尚未有针对纯化态地奥司明对胶质母细胞瘤的作用开展的相关研究。胶质母细胞瘤是一种致死率极高且生长迅速的脑肿瘤，亟需开发全新的治疗策略。本研究通过体外实验评估了该黄酮类化合物对抗胶质母细胞瘤细胞的效果。MTT实验结果显示，地奥司明可显著降低GBM95、GBM02及U87MG三种胶质母细胞瘤细胞的存活率，但对正常人星形胶质细胞无显著影响。波形蛋白（Vimentin）免疫染色结果表明，地奥司明可诱导GBM95与GBM02细胞发生形态学改变，使其体积缩小并呈现更为典型的多边形形态。地奥司明并未抑制GBM95和GBM02细胞的增殖，但通过TUNEL实验证实其可引发DNA片段化，并上调了这两种细胞中裂解型半胱天冬酶-3（cleaved caspase-3）的表达水平。综上，地奥司明可特异性地在肿瘤细胞中诱导半胱天冬酶依赖型细胞凋亡，因此有望成为治疗胶质母细胞瘤的潜在候选药物。