ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation

Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over last decade, validation novel 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 mechanisms underlying activity ConBr, lectin extracted from Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted death dependent upon carbohydrate recognition domain (CRD) structure. increased p38 MAPK JNK decreased ERK1/2 Akt phosphorylation. Moreover, mTORC1 phosphorylation associated accumulation autophagic markers, such as acidic vacuoles LC3 cleavage. Inhibition early steps autophagy 3-methyl-adenine (3-MA) partially protected whereas later inhibitor Chloroquine (CQ) had no protective effect cytotoxicity. also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, caspase-8 IETF-fmk attenuated induced death. Finally, did not show cytotoxicity against primary astrocytes, suggesting activity. In summary, our results indicate requires functional CRD activity, its MAPKs pathways modulation autophagy- caspase-8- • inhibits promotes by autophagy. ConBr-induced depends stimulates ERK, cells. displays cells compared astrocytes.