Glioma is a leading cause of central nervous system malignant tumor-associated deaths in the world. However, the molecular mechanisms for glioma progression are still unclear, lacking effective therapeutic strategies. Gomisin J (GomJ) is a derivative of lignan compound, and shows regulatory effects on virus, oxidative stress and tumor progression. However, the role of GomJ in the meditation of glioma progression has not been explored. In this study, we found that GomJ markedly reduced the proliferation of glioma cell lines. Mitochondrial apoptosis was highly induced by GomJ, as evidenced by the significantly up-regulated expression of cytoplastic Cyto-c and cleaved Caspase-3. In addition, mitochondrial membrane potential (MMP) and oxidative stress were highly triggered in GomJ-incubated glioma cells, accompanied with the glycolysis suppression. Importantly, we found that GomJ could dramatically reduce the expression of hexokinase II (HKII) in glioma cells. At the same time, the dissociation of HKII from voltage-dependent anion channel (VDAC) in mitochondria was markedly induced by GomJ, contributing to glycolytic repression. The in vivo experiments confirmed that GomJ obviously reduced the growth of glioma with HKII reduction and few side effects. Taken together, these results demonstrated that GomJ could inhibit the proliferation, induce apoptosis and restrain HKII-regulated glycolysis during glioma progression. Herein, GomJ with few toxicity might be served as a potential therapeutic strategy for the treatment of glioma in humans.

胶质瘤是世界上中枢神经系统恶性肿瘤相关死亡的主要原因。然而，胶质瘤进展的分子机制仍不清楚，缺乏有效的治疗策略。Gomisin J（GomJ）是木脂素化合物的衍生物，对病毒，氧化应激和肿瘤进展显示出调节作用。但是，尚未探讨GomJ在胶质瘤进展的冥想中的作用。在这项研究中，我们发现GomJ明显减少了胶质瘤细胞系的增殖。线粒体凋亡由GomJ高度诱导，这由细胞增生的Cyto-c和裂解的Caspase-3的表达明显上调所证明。此外，在GomJ培养的神经胶质瘤细胞中，线粒体膜电位（MMP）和氧化应激被高度触发，并伴有糖酵解抑制作用。重要的是，我们发现GomJ可以显着降低神经胶质瘤细胞中己糖激酶II（HKII）的表达。同时，GomJ明显诱导了线粒体中HKII从电压依赖性阴离子通道（VDAC）的解离，从而有助于糖酵解抑制。的体内实验证实，GomJ明显减少了神经胶质瘤的生长，并减少了HKII，且几乎没有副作用。两者合计，这些结果表明GomJ可以抑制胶质瘤进展过程中的增殖，诱导凋亡和抑制HKII调节糖酵解。在本文中，毒性低的GomJ可以作为治疗神经胶质瘤的潜在治疗策略。