Lectin from Dioclea violacea induces autophagy in U87 glioma cells

• Published in: International journal of biological macromolecules Vol. 134; pp. 660 - 672
• Main Authors: Nascimento, Ana Paula M., Wolin, Ingrid A.V., Welter, Priscilla G., Heinrich, Isabella A., Zanotto-Filho, Alfeu, Osterne, Vinicius J.S., Lossio, Claudia F., Silva, Mayara T.L., Nascimento, Kyria S., Cavada, Benildo S., Leal, Rodrigo B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2019
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - metabolism; Autophagy; Autophagy - drug effects; Caspase 3 - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Dioclea - chemistry; Dioclea violacea; Glioma - genetics; Glioma - metabolism; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondria - metabolism; mTOR; Plant Lectins - chemistry; Plant Lectins - isolation & purification; Plant Lectins - pharmacology; Rats; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; mTOR; Dioclea violacea; Autophagy
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2019.04.203

The antitumor activity of DVL, a lectin purified from Dioclea violacea seeds, on the U87 human glioma cell line was evaluated and compared with Canavalia ensiformis lectin (ConA). Treatment with DVL (10–100 μg/mL; 24–96 h) induced alterations in cell morphology, decreased cell numbers and clonogenic survival in a time- and concentration-dependent manner. DVL caused significant decreases in cell viability and impaired cell migration. Mechanistically, DVL treatment (12 h) disrupted mitochondrial electrochemical gradient, without ROS accumulation or caspase activation. In the absence of apoptosis, DVL (30–100 μg/mL), instead, induced autophagy, as detected by acridine orange staining and cleavage of LC3I. Inhibition of autophagy with 3-Methyladenine (3-MA) and Chloroquine partially abrogated DVL, but not ConA, cytotoxicity. The modulation of signaling pathways that orchestrate autophagic and cell survival processes were analyzed. DVL (30–100 μg/mL) decreased Akt, mTORC1 and ERK1/2 phosphorylation and augmented JNK(p54) and p38MAPK phosphorylation. DVL was more potent than ConA for most parameters analyzed. Even though both lectins showed cytotoxicity to glioma cells, they spared primary astrocyte cultures. The results suggest a selective antiglioma activity of DVL by inhibiting U87 glioma cell migration and proliferation and inducing cell death, partially associated with autophagy, and likely involving Akt and mTORC1 dephosphorylation. •Dioclea violacea lectin (DVL) caused significant decrease of U87 glioma cell viability and impaired cell migration.•DVL disrupted mitochondrial electrochemical gradient, without ROS accumulation or caspase activation.•DVL induced autophagy in U87 glioma cells by a mechanism likely involving Akt and mTORC1 inhibition.•Antiglioma activity of DVL was more potent than ConA.