Lectin from Dioclea violacea induces autophagy in U87 glioma cells

被引:17
作者
Nascimento, Ana Paula M. [1 ,2 ]
Wolin, Ingrid A. V. [1 ,2 ]
Welter, Priscilla G. [1 ,2 ]
Heinrich, Isabella A. [3 ]
Zanotto-Filho, Alfeu [4 ]
Osterne, Vinicius J. S. [5 ]
Lossio, Claudia F. [5 ]
Silva, Mayara T. L. [5 ]
Nascimento, Kyria S. [5 ]
Cavada, Benildo S. [5 ]
Leal, Rodrigo B. [1 ,2 ,3 ]
机构
[1] Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Bioquim, Campus Univ, BR-88040900 Florianopolis, SC, Brazil
[2] Univ Fed Santa Catarina, Ctr Ciencias Biol, Programa Posgrad Bioquim, Campus Univ, BR-88040900 Florianopolis, SC, Brazil
[3] Univ Fed Santa Catarina, Ctr Ciencias Biol, Programa Posgrad Neurociencias, Campus Univ, BR-88040900 Florianopolis, SC, Brazil
[4] Univ Fed Santa Catarina, Ctr Ciencias Biol, Programa Posgrad Farmacol, Dept Farmacol, Campus Univ, BR-88040900 Florianopolis, SC, Brazil
[5] Univ Fed Ceara, BioMolLab, Dept Bioquim & Biol Mol, BR-60020181 Fortaleza, Ceara, Brazil
关键词
Autophagy; Dioclea violacea; mTOR; CENTRAL-NERVOUS-SYSTEM; A-INDUCED AUTOPHAGY; CONCANAVALIN-A; APOPTOSIS; GLIOBLASTOMA; PROTEINS; ASSAY; PI3K/AKT/MTOR; ACTIVATION; MECHANISMS;
D O I
10.1016/j.ijbiomac.2019.04.203
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 ensiforrnis lectin (ConA). Treatment with DVL (10-100 mu g/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 mu g/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 pg/mL) decreased Akt, mTORC1 and ERK1/2 phosphorylation and augmented JNK(p54) and p38(MAPK) 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. (C) 2019 Elsevier B.V. All rights reserved.
引用
收藏
页码:660 / 672
页数:13
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