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The potent anti-cancer activity of Dioclea lasiocarpa lectin
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Gondim, Ana C. S., Romero-Canelón, Isolda, Sousa, Eduardo H.S., Blindauer, Claudia A., Butler, Jennifer S., Romero, Maria, Sanchez-Cano, Carlos, Sousa, Bruno L., Chaves, Renata P., Nagano, Celso S., Cavada, Benildo S. and Sadler, P. J. (2017) The potent anti-cancer activity of Dioclea lasiocarpa lectin. Journal of Inorganic Biochemistry, 175 . pp. 179-189. doi:10.1016/j.jinorgbio.2017.07.011
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Official URL: http://doi.org/10.1016/j.jinorgbio.2017.07.011
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.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QP Physiology | |||||||||
| Divisions: | Faculty of Science > Chemistry | |||||||||
| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Metalloproteins., Lectins., Cancer -- Prevention, Cancer -- Adjuvant treatment., Apoptosis. | |||||||||
| Journal or Publication Title: | Journal of Inorganic Biochemistry | |||||||||
| Publisher: | Elsevier BV | |||||||||
| ISSN: | 0162-0134 | |||||||||
| Official Date: | October 2017 | |||||||||
| Dates: |
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| Date of first compliant deposit: | 11 October 2017 | |||||||||
| Volume: | 175 | |||||||||
| Page Range: | pp. 179-189 | |||||||||
| DOI: | 10.1016/j.jinorgbio.2017.07.011 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access | |||||||||
| RIOXX Funder/Project Grant: |
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