The potent anti-cancer activity of  Dioclea lasiocarpa lectin

Ana C. S. Gondim; Isolda Romero-Canelón; Eduardo H.s. Sousa; Claudia A. Blindauer; Jennifer S. Butler; María J. Romero; Carlos Sanchez-Cano; Bruno L. Sousa; Renata P. Chaves; Celso S. Nagano; Benildo S. Cavada; Peter J. Sadler

doi:10.1016/j.jinorgbio.2017.07.011

The potent anti-cancer activity of Dioclea lasiocarpa lectin

Ana C. S. Gondim, Isolda Romero-Canelón, Eduardo H.s. Sousa, Claudia A. Blindauer, Jennifer S. Butler, María J. Romero, Carlos Sanchez-Cano, Bruno L. Sousa, Renata P. Chaves, Celso S. Nagano, Benildo S. Cavada, Peter J. Sadler

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Abstract

The lectin DLasiL was isolated from seeds of the Dioclea lasiocarpa collected from the northeast coast of Brazil and characterized for the first time by mass spectrometry, DNA sequencing, inductively coupled plasma-mass spectrometry, electron paramagnetic resonance, and fluorescence spectroscopy. The structure of DLasiL lectin obtained by homology modelling suggested strong conservation of the dinuclear Ca/Mn and sugar-binding sites, and dependence of the solvent accessibility of tryptophan-88 on the oligomerisation state of the protein. DLasiL showed highly potent (low nanomolar) antiproliferative activity against several human carcinoma cell lines including A2780 (ovarian), A549 (lung), MCF-7 (breast) and PC3 (prostate), and was as, or more, potent than the lectins ConBr (Canavalia brasiliensis), ConM (Canavalia maritima) and DSclerL (Dioclea sclerocarpa) against A2780 and PC3 cells. Interestingly, DLasiL lectin caused a G2/M arrest in A2780 cells after 24 h exposure, activating caspase 9 and delaying the on-set of apoptosis. Confocal microscopy showed that fluorescently-labelled DLasiL localized around the nuclei of A2780 cells at lectin doses of 0.5–2 × IC50 and gave rise to enlarged nuclei and spreading of the cells at high doses. These data reveal the interesting antiproliferative activity of DLasiL lectin, and suggest that further investigations to explore the potential of DLasiL as a new anticancer agent are warranted.

Original language	English
Pages (from-to)	179-189
Journal	Journal of Inorganic Biochemistry
Volume	175
Early online date	16 Jul 2017
DOIs	https://doi.org/10.1016/j.jinorgbio.2017.07.011
Publication status	Published - 1 Oct 2017

Keywords

metalloprotein
legume lectin
homology model
anticancer
apoptosis

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Gondim_et_al_The_potent_anti-cancer_activity_Journal_of_Inorganic_Biochemistry_2017
Published in Journal of Inorganic Chemistry on 16/07/2017 DOI: 10.1016/j.jinorgbio.2017.07.011
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https://www.sciencedirect.com/science/article/pii/S016201341730209XLicence: Creative Commons: Attribution (CC BY)

Cite this

@article{9115f51fbdf841bc82a6df8249809790,

title = "The potent anti-cancer activity of Dioclea lasiocarpa lectin",

abstract = "The lectin DLasiL was isolated from seeds of the Dioclea lasiocarpa collected from the northeast coast of Brazil and characterized for the first time by mass spectrometry, DNA sequencing, inductively coupled plasma-mass spectrometry, electron paramagnetic resonance, and fluorescence spectroscopy. The structure of DLasiL lectin obtained by homology modelling suggested strong conservation of the dinuclear Ca/Mn and sugar-binding sites, and dependence of the solvent accessibility of tryptophan-88 on the oligomerisation state of the protein. DLasiL showed highly potent (low nanomolar) antiproliferative activity against several human carcinoma cell lines including A2780 (ovarian), A549 (lung), MCF-7 (breast) and PC3 (prostate), and was as, or more, potent than the lectins ConBr (Canavalia brasiliensis), ConM (Canavalia maritima) and DSclerL (Dioclea sclerocarpa) against A2780 and PC3 cells. Interestingly, DLasiL lectin caused a G2/M arrest in A2780 cells after 24 h exposure, activating caspase 9 and delaying the on-set of apoptosis. Confocal microscopy showed that fluorescently-labelled DLasiL localized around the nuclei of A2780 cells at lectin doses of 0.5–2 × IC50 and gave rise to enlarged nuclei and spreading of the cells at high doses. These data reveal the interesting antiproliferative activity of DLasiL lectin, and suggest that further investigations to explore the potential of DLasiL as a new anticancer agent are warranted.",

keywords = "metalloprotein , legume lectin , homology model , anticancer , apoptosis",

author = "Gondim, {Ana C. S.} and Isolda Romero-Canel{\'o}n and Sousa, {Eduardo H.s.} and Blindauer, {Claudia A.} and Butler, {Jennifer S.} and Romero, {Mar{\'i}a J.} and Carlos Sanchez-Cano and Sousa, {Bruno L.} and Chaves, {Renata P.} and Nagano, {Celso S.} and Cavada, {Benildo S.} and Sadler, {Peter J.}",

year = "2017",

month = oct,

day = "1",

doi = "10.1016/j.jinorgbio.2017.07.011",

language = "English",

volume = "175",

pages = "179--189",

journal = "Journal of Inorganic Biochemistry",

issn = "0162-0134",

publisher = "Elsevier",

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T1 - The potent anti-cancer activity of Dioclea lasiocarpa lectin

AU - Gondim, Ana C. S.

AU - Romero-Canelón, Isolda

AU - Sousa, Eduardo H.s.

AU - Blindauer, Claudia A.

AU - Butler, Jennifer S.

AU - Romero, María J.

AU - Sanchez-Cano, Carlos

AU - Sousa, Bruno L.

AU - Chaves, Renata P.

AU - Nagano, Celso S.

AU - Cavada, Benildo S.

AU - Sadler, Peter J.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - The lectin DLasiL was isolated from seeds of the Dioclea lasiocarpa collected from the northeast coast of Brazil and characterized for the first time by mass spectrometry, DNA sequencing, inductively coupled plasma-mass spectrometry, electron paramagnetic resonance, and fluorescence spectroscopy. The structure of DLasiL lectin obtained by homology modelling suggested strong conservation of the dinuclear Ca/Mn and sugar-binding sites, and dependence of the solvent accessibility of tryptophan-88 on the oligomerisation state of the protein. DLasiL showed highly potent (low nanomolar) antiproliferative activity against several human carcinoma cell lines including A2780 (ovarian), A549 (lung), MCF-7 (breast) and PC3 (prostate), and was as, or more, potent than the lectins ConBr (Canavalia brasiliensis), ConM (Canavalia maritima) and DSclerL (Dioclea sclerocarpa) against A2780 and PC3 cells. Interestingly, DLasiL lectin caused a G2/M arrest in A2780 cells after 24 h exposure, activating caspase 9 and delaying the on-set of apoptosis. Confocal microscopy showed that fluorescently-labelled DLasiL localized around the nuclei of A2780 cells at lectin doses of 0.5–2 × IC50 and gave rise to enlarged nuclei and spreading of the cells at high doses. These data reveal the interesting antiproliferative activity of DLasiL lectin, and suggest that further investigations to explore the potential of DLasiL as a new anticancer agent are warranted.

AB - The lectin DLasiL was isolated from seeds of the Dioclea lasiocarpa collected from the northeast coast of Brazil and characterized for the first time by mass spectrometry, DNA sequencing, inductively coupled plasma-mass spectrometry, electron paramagnetic resonance, and fluorescence spectroscopy. The structure of DLasiL lectin obtained by homology modelling suggested strong conservation of the dinuclear Ca/Mn and sugar-binding sites, and dependence of the solvent accessibility of tryptophan-88 on the oligomerisation state of the protein. DLasiL showed highly potent (low nanomolar) antiproliferative activity against several human carcinoma cell lines including A2780 (ovarian), A549 (lung), MCF-7 (breast) and PC3 (prostate), and was as, or more, potent than the lectins ConBr (Canavalia brasiliensis), ConM (Canavalia maritima) and DSclerL (Dioclea sclerocarpa) against A2780 and PC3 cells. Interestingly, DLasiL lectin caused a G2/M arrest in A2780 cells after 24 h exposure, activating caspase 9 and delaying the on-set of apoptosis. Confocal microscopy showed that fluorescently-labelled DLasiL localized around the nuclei of A2780 cells at lectin doses of 0.5–2 × IC50 and gave rise to enlarged nuclei and spreading of the cells at high doses. These data reveal the interesting antiproliferative activity of DLasiL lectin, and suggest that further investigations to explore the potential of DLasiL as a new anticancer agent are warranted.

KW - metalloprotein

KW - legume lectin

KW - homology model

KW - anticancer

KW - apoptosis

U2 - 10.1016/j.jinorgbio.2017.07.011

DO - 10.1016/j.jinorgbio.2017.07.011

M3 - Article

SN - 0162-0134

VL - 175

SP - 179

EP - 189

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

ER -