Induction of Autophagy by Concanavalin A and its Application in Anti-Tumor Therapy

Lei, Huan Yao; Chang, Chih Peng

doi:10.4161/auto.4280

Cited by 70 publications

(43 citation statements)

References 21 publications

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“…However, as with Con A, Morniga M might trigger other cell death mechanisms. Indeed, it was demonstrated recently that Con A induces a caspase-independent cell death including autophagy [37,38]. As apoptosis and other kinds of cell death share the same characteristics in terms of Annexin V positivity [39], our present results cannot discriminate between both types of cell death.…”

Section: Discussionmentioning

confidence: 50%

Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death

Benoist

Culerrier

Poiroux

et al. 2009

Journal of Leukocyte Biology

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Plant lectins displaying similar single sugar-binding specificity and identical molecular structure might present various biological effects. To explore this possibility, the effects on human lymphocytes of two mannose-specific and structurally closely related lectins, Morniga M from Morus nigra and artocarpin from Artocarpus integrifolia were investigated. In silico analysis revealed that Morniga M presents a more largely open carbohydrate-binding cavity than artocarpin, probably allowing interactions with a broader spectrum of carbohydrate moieties. In vitro, Morniga M interacted strongly with the lymphocyte surface and was uptaken quickly by cells. Morniga M and artocarpin triggered the proliferation and activation of human T and NK lymphocytes. A minority of B lymphocytes was activated in artocarpin-treated culture, whereas Morniga M favored the emergence of CD4ϩ CD8ϩ T lymphocytes. Moreover, cell death occurred in activated PBMC, activated T lymphocytes, and Jurkat T leukemia cells incubated with Morniga M only. The biological effects of both lectins were dependent on carbohydrate recognition. The Morniga M-induced cell death resulted, at least in part, from caspase-dependent apoptosis and FADD-dependent receptor-mediated cell death. Finally, Morniga M, but not artocarpin, triggered AICD of T lymphocytes. In conclusion, both lectins trigger lymphocyte activation, but only Morniga M induces cell death. In spite of similar in vitro mannose-binding specificities and virtually identical structure, only Morniga M probably interacts with carbohydrate moieties bound to molecules able to induce cell death. The present data suggest that subtle alterations in N-glycans can distinguish activation and cell death molecules at the lymphocyte surface.

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Section: Discussionmentioning

confidence: 50%

Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death

Benoist

Culerrier

Poiroux

et al. 2009

Journal of Leukocyte Biology

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“…The cellular ultrastructural morphology was observed without ConA (Control) or with 20μg/ml ConA for 24 h (ConA) under electron microscopy (a). The HepG2 cells were treated with 25μg/ml ConA for 12, 24, or 36 h, and apoptotic and necrotic ratio was measured by LDH activity-based assay (x±SD, n=3; b) that ConA is cytotoxic or inhibitory to hepatoma cells, which can be mediated by a mitochondrial autophagic pathway [12,30]. However, the typical apoptosis was not observed in ConA-treated cancer cells [30].…”

Section: Discussionmentioning

confidence: 99%

In Silico and Experimental Studies of Concanavalin A: Insights into Its Antiproliferative Activity and Apoptotic Mechanism

Liu

Ding

et al. 2009

Appl Biochem Biotechnol

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Concanavalin A (ConA), a mannose/glucose-binding legume lectin, has been reported to induce tumor cell death via a mitochondria-mediated autophagic pathway; however, the precise mechanism by which induces cell death remains to be discovered. In this study, we simulated the three-dimensional structure of ConA monomer, its dimer, and tetramer forms and reported its molecular dynamics simulations and phylogenetic analysis. Subsequently, we showed that ConA possessed remarkable antiproliferative effects on HepG2 cells. Further data showed that there was a link among its hemagglutinating, sugar-binding, and antiproliferative activities. In addition, we found that ConA induced apoptosis in HepG2 cells. Then, we demonstrated that the treatment of ConA caused mitochondrial transmembrane potential (MMP) collapse, cytochrome c release, and activation of caspase. In conclusion, we demonstrate that there is a positive correlation between carbohydrate-binding activity and antiproliferative activity of ConA. In addition, we confirm that ConA induces HepG2 cell death through a mitochondrial apoptotic pathway.

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“…La trehalosa es un osmolito que puede ser utilizado como crioprotector, o bien el diglicerol fosfato, producido por Arqueolobus fulgidus, que es un potente estabilizador de proteínas frente a la temperatura (Margesin y Schinner, 2001). Otro de los productos utilizados como moléculas para el reconocimiento celular son las lectinas, especialmente la concanavalina A, producidas por arqueobacterias halófilas que se usan como indicadores de las modificaciones de la superficie celular en la detección de células malignas (Lei y Chang, 2007).…”

Section: Biotecnología Y Ciencias Agropecuariasunclassified

Utilización de microorganismos de ambientes extremos y sus productos en el desarrollo biotecnológico

2016

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La biotecnología representa una alternativa viable para el desarrollo industrial sustentable, ya que provee las herramientas necesarias para adaptar y modificar organismos, productos, sistemas y procesos naturales para mejorar el quehacer industrial, haciéndolo más rentable, diverso y amigable con el entorno de lo que pueden ser los procesos químicos y físicos tradicionales. En este sentido, los microorganismos extremófilos constituyen la opción más prometedora como fuente de biomoléculas con capacidad biocatalizadora, capaces de soportar condiciones drásticas de proceso y cuyo uso comercial puede conducir a la sustentabilidad industrial.

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Induction of Autophagy by Concanavalin A and its Application in Anti-Tumor Therapy

Cited by 70 publications

References 21 publications

Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death

Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death

In Silico and Experimental Studies of Concanavalin A: Insights into Its Antiproliferative Activity and Apoptotic Mechanism

Utilización de microorganismos de ambientes extremos y sus productos en el desarrollo biotecnológico

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