Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38^MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.

多形性胶质母细胞瘤是胶质瘤中最具侵略性的一种，治疗效果有限，预后差。尽管在过去十年中取得了一些进展，但是新型和选择性抗神经胶质瘤药物的验证仍然是临床药理学中的一个挑战。先前的研究表明，豆科植物凝集素可能发挥多种生物学作用，包括抗肿瘤特性。因此，本研究旨在评估ConBr的抗神经胶质瘤活性的机制，ConBr是从巴西Canavalia种子中提取的一种凝集素。较低浓度的ConBr抑制C6胶质瘤细胞迁移，而较高的水平则依赖于碳水化合物识别域（CRD）结构促进细胞死亡。ConBr增加p38 ^MAPK和JNK和减少的ERK1 / 2和Akt磷酸化。此外，ConBr抑制了mTORC1磷酸化与自噬标记物（例如酸性液泡和LC3裂解）的积累有关。用3-甲基腺嘌呤（3-MA）抑制自噬的早期步骤部分受到保护，而后来的自噬抑制剂氯喹（CQ）对ConBr细胞毒性没有保护作用。ConBr还增强了caspase-3激活，而不会影响线粒体功能。值得注意的是，caspase-8抑制剂IETF-fmk减弱了ConBr诱导的自噬和C6胶质瘤细胞死亡。最后，ConBr没有显示出对原代星形胶质细胞的细胞毒性，表明具有选择性的抗神经胶质瘤活性。总之，我们的结果表明，ConBr需要功能性CRD凝集素域才能发挥抗神经胶质瘤活性，