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1.
Histochem Cell Biol ; 160(5): 435-452, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37535087

RESUMO

Urinary bladder cancer can be treated by intravesical application of therapeutic agents, but the specific targeting of cancer urothelial cells and the endocytotic pathways of the agents are not known. During carcinogenesis, the superficial urothelial cells exhibit changes in sugar residues on the apical plasma membranes. This can be exploited for selective targeting from the luminal side of the bladder. Here we show that the plant lectins Jacalin (from Artocarpus integrifolia), ACA (from Amaranthus caudatus) and DSA (from Datura stramonium) selectively bind to the apical plasma membrane of low- (RT4) and high-grade (T24) cancer urothelial cells in vitro and urothelial tumours ex vivo. The amount of lectin binding was significantly different between RT4 and T24 cells. Endocytosis of lectins was observed only in cancer urothelial cells and not in normal urothelial cells. Transmission electron microscopy analysis showed macropinosomes, endosome-like vesicles and multivesicular bodies filled with lectins in RT4 and T24 cells and also in cells of urothelial tumours ex vivo. Endocytosis of Jacalin and ACA in cancer cells was decreased in vitro after addition of inhibitor of macropinocytosis 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and increased after stimulation of macropinocytosis with epidermal growth factor (EGF). Clathrin, caveolin and flotillin did not colocalise with lectins. These results confirm that the predominant mechanism of lectin endocytosis in cancer urothelial cells is macropinocytosis. Therefore, we propose that lectins in combination with conjugated therapeutic agents are promising tools for improved intravesical therapy by targeting cancer cells.


Assuntos
Lectinas , Neoplasias da Bexiga Urinária , Humanos , Lectinas/metabolismo , Neoplasias da Bexiga Urinária/patologia , Endocitose/fisiologia , Bexiga Urinária/metabolismo , Endossomos/metabolismo , Lectinas de Plantas/farmacologia , Lectinas de Plantas/metabolismo , Lectinas de Plantas/uso terapêutico
2.
Cell Commun Signal ; 20(1): 167, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289525

RESUMO

Concanavalin A (ConA), the most studied plant lectin, has been known as a potent anti-neoplastic agent for a long time. Since initial reports on its capacity to kill cancer cells, much attention has been devoted to unveiling the lectin's exact molecular mechanism. It has been revealed that ConA can bind to several receptors on cancerous and normal cells and modulate the related signaling cascades. The most studied host receptor for ConA is MT1-MMP, responsible for most of the lectin's modulations, ranging from activating immune cells to killing tumor cells. In this study, in addition to studying the effect of ConA on signaling and immune cell function, we will focus on the most up-to-date advancements that unraveled the molecular mechanisms by which ConA can induce autophagy and apoptosis in various cancer cell types, where it has been found that P73 and JAK/STAT3 are the leading players. Moreover, we further discuss the main signaling molecules causing liver injury as the most significant side effect of the lectin injection. Altogether, these findings may shed light on the complex signaling pathways controlling the diverse responses created via ConA treatment, thereby modulating these complex networks to create more potent lectin-based cancer therapy. Video Abstract.


Assuntos
Lectinas , Neoplasias , Humanos , Concanavalina A/farmacologia , Concanavalina A/uso terapêutico , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/uso terapêutico , Neoplasias/tratamento farmacológico , Lectinas de Plantas/uso terapêutico
3.
J Infect Dis ; 221(Supplement_4): S480-S492, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32037447

RESUMO

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.


Assuntos
Antivirais/farmacologia , Infecções por Henipavirus/tratamento farmacológico , Vírus Nipah/efeitos dos fármacos , Lectinas de Plantas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Animais , Antivirais/uso terapêutico , Chlorocebus aethiops , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Células HEK293 , Células HeLa , Infecções por Henipavirus/virologia , Humanos , Mesocricetus , Vírus Nipah/isolamento & purificação , Lectinas de Plantas/uso terapêutico , Células Vero
4.
Pharmacol Res ; 144: 8-18, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30951812

RESUMO

Plant lectins are non-immunoglobin in nature and bind to the carbohydrate moiety of the glycoconjugates without altering any of the recognized glycosyl ligands. Plant lectins have found applications as cancer biomarkers for recognizing the malignant tumor cells for the diagnosis and prognosis of cancer. Interestingly, plant lectins contribute to inducing cell death through autophagy and apoptosis, indicating their potential implication in cancer inhibitory mechanism. In the present review, anticancer activities of major plant lectins have been documented, with a detailed focus on the signaling circuit for the possible molecular targeted cancer therapy. In this context, several lectins have exhibited preclinical and clinical significance, driving toward therapeutic potential in cancer treatment. Moreover, several plant lectins induce immunomodulatory activities, and therefore, novel strategies have been established from preclinical and clinical investigations for the development of combinatorial treatment consisting of immunotherapy along with other anticancer therapies. Although the application of plant lectins in cancer is still in very preliminary stage, advanced high-throughput technology could pave the way for the development of lectin-based complimentary medicine for cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Lectinas de Plantas/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Neoplasias/imunologia , Neoplasias/patologia , Lectinas de Plantas/farmacologia
5.
Int J Mol Sci ; 20(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547569

RESUMO

The development of natural phospholipids for nanostructured drug delivery systems has attracted much attention in the past decades. Lecithin that was derived from naturally occurring in soybeans (SL) has introduced some auspicious accomplishments to the drug carrying aspect, like effectual encapsulation, controlled release, and successful delivery of the curative factors to intracellular regions in which they procure these properties from their flexible physicochemical and biophysical properties, such as large aqueous center and biocompatible lipid, self-assembly, tunable properties, and high loading capacity. Despite the almost perfect properties as a drug carrier, liposome is known to be quite quickly eliminated from the body systems. The surface modification of liposomes has been investigated in many studies to overcome this drawback. In this review, we intensively discussed the surface-modified liposomes that enhancing the targeting, cellular uptake, and therapeutic response. Moreover, the recent applications of soy lecithin-derived liposome, focusing on cancer treatment, brain targeting, and vaccinology, are also summarized.


Assuntos
Antineoplásicos/uso terapêutico , Encéfalo , Neoplasias , Lectinas de Plantas/uso terapêutico , Proteínas de Soja/uso terapêutico , Vacinas/uso terapêutico , Animais , Antineoplásicos/química , Encéfalo/metabolismo , Encéfalo/patologia , Humanos , Lipossomos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Lectinas de Plantas/química , Proteínas de Soja/química , Propriedades de Superfície , Vacinas/química
6.
Int J Mol Sci ; 20(12)2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31234551

RESUMO

Experiments conducted in vitro and in vivo, as well as some preclinical trials for cancer therapeutics, support the antineoplastic properties of lectins. A screening of antitumoral activity on HT29 colon cancer cells, based on polypeptide characterization and specific lectin binding to HT29 cells membrane receptors, was performed in order to assess the bioactivities present in four Mediterranean plant species: Juniperus oxycedrus subsp. oxycedrus, Juniperus oxycedrus subsp. badia, Arbutus unedo and Corema album. Total leaf proteins from each species were evaluated with respect to cell viability and inhibitory activities on HT29 cells (cell migration, matrix metalloproteinase -MMP proteolytic activities). A discussion is presented on a possible mechanism justifying the specific binding of lectins to HT29 cell receptors. All species revealed the presence of proteins with affinity to HT29 cell glycosylated receptors, possibly explaining the differential antitumor activity exhibited by the two most promising species, Juniperus oxycedrus subsp. badia and Arbutus unedo.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Lectinas de Plantas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sobrevivência Celular , Ericaceae/química , Células HT29 , Humanos , Juniperus/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Lectinas de Plantas/uso terapêutico
7.
Mol Carcinog ; 56(11): 2400-2413, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28543759

RESUMO

Oral cancer, a type of head and neck cancer, is ranked as one of the top most malignancies in India. Herein, we evaluated the anticancer efficacy of Abrus agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)-mediated ATM-p73 dependent pathway in FaDu cells. AGG-induced ROS accumulation was identified as the major mechanism regulating apoptosis, DNA damage and DNA-damage response, which were significantly reversed by ROS scavenger N-acetylcysteine (NAC). Moreover, AGG was found to interact with mitochondrial manganese-dependent superoxide dismutase that might inhibit its activity and increase ROS in FaDu cells. In oral cancer p53 is mutated, thus we focused on p73; AGG resulted in p73 upregulation and knock down of p73 caused a decrease in AGG-induced apoptosis. Interestingly, AGG-dependent p73 expression was found to be regulated by ROS, which was reversed by NAC treatment. A reduction in the level of p73 in AGG-treated shATM cells was found to be associated with a decreased apoptosis. Moreover, administration of AGG (50 µg/kg body weight) significantly inhibited the growth of FaDu xenografts in athymic nude mice. In immunohistochemical analysis, the xenografts from AGG-treated mice displayed a decrease in PCNA expression and an increase in caspase-3 activation as compared to the controls. In conclusion, we established a connection among ROS, ATM and p73 in AGG-induced apoptosis, which might be useful in enhancing the therapeutic targeting of p53 deficient oral squamous cell carcinoma.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Dano ao DNA/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Lectinas de Plantas/uso terapêutico , Proteína Tumoral p73/metabolismo , Abrus/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Modelos Moleculares , Boca/efeitos dos fármacos , Boca/metabolismo , Boca/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Lectinas de Plantas/química , Lectinas de Plantas/farmacologia , Espécies Reativas de Oxigênio/metabolismo
8.
Neurochem Res ; 42(2): 347-359, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27747481

RESUMO

Lectins are proteins that bind cellular glycans and can modulate various neuronal functions. We have evaluated the neuroprotective effect of ConBr, a lectin purified from the seeds of Canavalia brasiliensis in a model of rat organotypic hippocampal cultures (OHCs) exposed to oxygen and glucose deprivation (OGD). OGD for 15 min followed by 24 h re-oxygenation significantly increased cell death, caused mitochondrial depolarization and increased reactive oxygen species (ROS) in CA1 region of OHCs. ConBr (0.1 µg/mL) added during the re-oxygenation period counteracted cell death, mitochondrial depolarization and overproduction of ROS induced by OGD. Moreover, ConBr restored the levels of Akt and ERK1 phosphorylation that were reduced by OGD. Modulation of intracellular Ca2+ by ConBr was evaluated in isolated hippocampal neurons loaded with the fluorescent calcium dye Fluo-4/AM. ConBr (0.1 and 1 µg/mL) reduced by 25-30 % the Ca2+ increment induced by 70 mM K+. A sub effective concentration of ConBr (0.01 µg/mL) together with a sub effective concentration of the L-type calcium channel antagonist nifedipine (0.3 µM) conferred a synergic neuroprotective effect in OHCs subjected to OGD. In conclusion, ConBr provides OHCs neuroprotection against OGD. The mechanism was not fully addressed but it may involve modulation of L-type voltage-gated Ca2+ channels by ConBr.


Assuntos
Isquemia Encefálica/metabolismo , Canais de Cálcio/metabolismo , Canavalia , Hipocampo/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Lectinas de Plantas/uso terapêutico , Animais , Isquemia Encefálica/prevenção & controle , Células Cultivadas , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Técnicas de Cultura de Órgãos , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/farmacologia , Ratos , Ratos Sprague-Dawley , Sementes
9.
BMC Complement Altern Med ; 17(1): 237, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28454538

RESUMO

BACKGROUND: The hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (Viscum album L.). Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo. METHODS: We recreated a total mistletoe effect (viscumTT) by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilised with cyclodextrins and analysed the effects of viscumTT and the single extracts on TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling. RESULTS: Treatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism of action of viscum, TT and viscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded protein response. While viscum and viscumTT extract treatment indicate response to oxidative stress and activation of stress-mediated MAPK signalling, TT extract treatment suggests the involvement of TLR signalling and autophagy. CONCLUSIONS: Since the combinatory extract viscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Lectinas de Plantas/farmacologia , Proteínas de Plantas/farmacologia , Sarcoma de Ewing/metabolismo , Triterpenos/farmacologia , Viscum album/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Autofagia , Proliferação de Células , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas de Neoplasias/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Triterpenos Pentacíclicos , Fitoterapia , Extratos Vegetais/uso terapêutico , Lectinas de Plantas/uso terapêutico , Proteínas de Plantas/uso terapêutico , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteoma , Proteômica , Sarcoma de Ewing/tratamento farmacológico , Transdução de Sinais , Transcriptoma , Triterpenos/uso terapêutico , Células Tumorais Cultivadas , Ácido Betulínico
10.
Int J Mol Sci ; 18(7)2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28671623

RESUMO

Digestive system cancers-those of the esophagus, stomach, small intestine, colon-rectum, liver, and pancreas-are highly related to genetics and lifestyle. Most are considered highly mortal due to the frequency of late diagnosis, usually in advanced stages, caused by the absence of symptoms or masked by other pathologies. Different tools are being investigated in the search of a more precise diagnosis and treatment. Plant lectins have been studied because of their ability to recognize and bind to carbohydrates, exerting a variety of biological activities on animal cells, including anticancer activities. The present report integrates existing information on the activity of plant lectins on various types of digestive system cancers, and surveys the current state of research into their properties for diagnosis and selective treatment.


Assuntos
Neoplasias do Sistema Digestório/tratamento farmacológico , Lectinas de Plantas/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Tecnologia Biomédica , Humanos
11.
Invest New Drugs ; 33(1): 1-11, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25200916

RESUMO

BACKGROUND: The incidence and mortality of hepatocellular carcinoma (HCC) remain high worldwide. Drug screening from natural plants is one of the potential therapeutic approaches on HCC. METHODS: The antitumor effect of momordica charantia lectin (MCL) was examined, using MTT, colony formation, AnnexinV/PI staining, western blot and animal model. RESULTS: MCL treatment induced G2/M phase arrest, autophagy, DNA fragmentation, mitochondrial injury, and subsequently cell apoptosis in HCC cells. Activation of caspase and MAPK pathway was involved in MCL-induced apoptosis. In vitro and in vivo studies showed that up-regulation of truncated Bid (tBid) upon MCL treatment. Correlation analysis revealed that Bid expression was reversely associated with the IC50 of MCL. Bid suppression using Bid siRNA, BI-6C9 (Bid inhibitor) and Z-IETD-FMK (caspase 8 inhibitor) dramatically attenuated MCL-induced cell proliferation inhibition, caspase 3 activation, ΔΨm depolarization and apoptosis. In addition, combination of MCL and sorafenib exerted stronger lethal activity towards HCC in vitro and in vivo. CONCLUSION: Our data show that the natural compound MCL manifests antitumor activities towards HCC and therefore suggest MCL as a promising chemotherapeutic agent.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Momordica charantia , Lectinas de Plantas/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/fisiopatologia , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Nus , Lectinas de Plantas/farmacologia , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Antimicrob Agents Chemother ; 58(1): 120-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24145548

RESUMO

Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.


Assuntos
Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/farmacocinética , Antivirais/sangue , Antivirais/farmacocinética , Lectinas de Plantas/sangue , Lectinas de Plantas/farmacocinética , Animais , Fármacos Anti-HIV/uso terapêutico , Antivirais/uso terapêutico , Feminino , Cobaias , Proteína gp120 do Envelope de HIV/metabolismo , Imunoensaio , Camundongos , Camundongos Endogâmicos BALB C , Lectinas de Plantas/uso terapêutico
13.
Acta Pharmacol Sin ; 35(6): 814-24, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24793310

RESUMO

AIM: Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. METHODS: Cell proliferation, DNA fragmentation, Annexin V binding, immunocytofluorescence, Western blotting, caspase activity assays and luciferase assays were performed to evaluate AGG in human liver cancer cells HepG2. Immunohistochemical staining and TUNEL expression were studied in tumor samples of HepG2-xenografted nude mice. RESULTS: AGG induced apoptosis in HepG2 cells in a dose- and time-dependent manner. AGG-treated HepG2 cells demonstrated an increase in caspase 3/7, 8 and 9 activities and a sharp decrease in the Bcl-2/Bax ratio, indicating activation of a caspase cascade. Co-treatment of HepG2 cells with AGG and a caspase inhibitor or treatment of AGG in Bax knockout HepG2 cells decreased the caspase 3/7 activity in comparison to HepG2 cells exposed only to AGG. Moreover, AGG decreased the expression of Hsp90 and suppressed Akt phosphorylation and NF-κB expression in HepG2 cells. Finally, AGG treatment significantly reduced tumor growth in nude mice bearing HepG2 xenografts, increased TUNEL expression and decreased CD-31 and Ki-67 expression compared to levels observed in the untreated control mice bearing HepG2 cells. CONCLUSION: AGG inhibits the growth and progression of HepG2 cells by inducing caspase-mediated cell death. The agglutinin could be an alternative natural remedy for the treatment of human hepatocellular carcinomas.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Lectinas de Plantas/uso terapêutico , Abrus/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos Nus , Lectinas de Plantas/química , Lectinas de Plantas/farmacologia
14.
Biochimie ; 202: 136-145, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35952948

RESUMO

Since the early discovery of plant lectins at the end of the 19th century, and the finding that they could agglutinate erythrocytes and precipitate glycans from their solutions, many applications and biological roles have been described for these proteins. Later, the observed erythrocytes clumping features were attributed to the lectin-cell surface glycoconjugates recognition. Neoplastic transformation leads to various cellular alterations which impact the growth of the cell and its persistence, among which is the mutation in the outer surface glycosylation signatures. Quite a few lectins have been found to act as excellent biomarkers for cancer diagnosis while some were presented with antiproliferative activity that initiated by lectin binding to the respective glycocalyx receptors. These properties are blocked by the hapten sugar that is competing for the lectin affinity binding site. In vitro investigations of lectin-cancer cell's glycocalyx interactions lead to a series of immunological reactions that result in autophagy or apoptosis of the transformed cells. Mistletoe lectin, an agglutinin purified from the European Viscum album is the first plant lectin employed in the treatment of cancer to enter into the clinical trial phases. The entrapment of lectin in nanoparticles besides other techniques to promote bioavailability and stability have also been recently studied. This review summarizes our up-to-date understanding of the future applications of plant lectins in cancer prognosis and diagnosis. With the provision of many examples of lectins that exhibit anti-neoplastic properties.


Assuntos
Antineoplásicos , Produtos Biológicos , Lectinas de Plantas/farmacologia , Lectinas de Plantas/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Lectinas/uso terapêutico , Apoptose
15.
Biomed Pharmacother ; 146: 112507, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34891122

RESUMO

Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19. Lectins have binding affinity to the glycans of SARS-COV-2 Spike glycoprotein that has N-glycosylation sites. Apart from this, the complement lectin pathway is a "first line host defense" against the viral infection that is activated by mannose-binding lectins. Mannose-binding lectins deficiency in serum influences innate immunity of the host and facilitates infectious diseases including COVID-19. Our accumulated evidence obtained from scientific databases particularly PubMed and Google Scholar databases indicate that mannose-specific/mannose-binding lectins (MBL) have potent efficacies like anti-infectivity, complement cascade induction, immunoadjuvants, DC-SIGN antagonists, or glycomimetic approach, which can prove useful in the strategy of COVID-19 combat along with the glycobiological aspects of SARS-CoV-2 infections and antiviral immunity. For example, plant-derived mannose-specific lectins BanLac, FRIL, Lentil, and GRFT from red algae can inhibit and neutralize SARS-CoV-2 infectivity, as confirmed with in-vitro, in-vivo, and in-silico assessments. Furthermore, Bangladesh has a noteworthy resource of antiviral medicinal plants as well as plant lectins. Intensifying research on the antiviral plant lectins, adopting a glyco-biotechnological approach, and with deeper insights into the "glycovirological" aspects may result in the designing of alternative and potent blueprints against the 21st century's biological pandemic of SARS-CoV-2 causing COVID-19.


Assuntos
Antivirais/uso terapêutico , Terapia Biológica/métodos , COVID-19/prevenção & controle , Erradicação de Doenças/métodos , Lectinas de Plantas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/isolamento & purificação , Antivirais/farmacologia , Terapia Biológica/tendências , COVID-19/epidemiologia , Erradicação de Doenças/tendências , Humanos , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/farmacologia
16.
Exp Parasitol ; 128(1): 61-7, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21320493

RESUMO

Antiparasitic effect of a lectin isolated from Synadenium carinatum latex (ScLL) was evaluated against Leishmania (Leishmania) amazonensis promastigotes/amastigotes. Pretreatment of murine inflammatory peritoneal macrophages with ScLL reduced by 65.5% the association index of macrophages and L. (L) amazonensis promastigotes. Expression of cytokines (IL-12, IL-1 and TNF-α) was detected in infected macrophages pretreated with ScLL (10µg/mL). ScLL also reduced the growth of L. (L) amazonensis amastigote intracellular forms, showing no in vitro cytotoxic effects in mammalian host cells. ScLL treatment in infected murine inflammatory peritoneal macrophages did not induce nitric oxide production, suggesting that a nitric oxide independent pathway is activated to decrease the number of intracellular Leishmania.


Assuntos
Euphorbiaceae/química , Látex/farmacologia , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Macrófagos Peritoneais/parasitologia , Lectinas de Plantas/farmacologia , Animais , Células Cultivadas , Citocinas/biossíntese , Citocinas/genética , Látex/uso terapêutico , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Óxido Nítrico/genética , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Lectinas de Plantas/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Front Immunol ; 12: 582556, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262553

RESUMO

Introduction: Several months ago, Chinese authorities identified an atypical pneumonia in Wuhan city, province of Hubei (China) caused by a novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19". Evidence Acquisition: Several approaches are currently underway for the treatment of this disease, but a specific cure remains to be established. Evidence Synthesis: This review will describe how the use of selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients. Conclusions: Even if a specific and effective cure for COVID-19 still has some way to go, selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients.


Assuntos
COVID-19/complicações , COVID-19/prevenção & controle , Suplementos Nutricionais , SARS-CoV-2 , Berberina/uso terapêutico , COVID-19/epidemiologia , COVID-19/virologia , China/epidemiologia , Ácidos Graxos Ômega-3/uso terapêutico , Polissacarídeos Fúngicos/uso terapêutico , Humanos , Lactoferrina/uso terapêutico , Minerais/uso terapêutico , Lectinas de Plantas/uso terapêutico , Polifenóis/uso terapêutico , Alimentos de Soja , Vitaminas/uso terapêutico
18.
Int J Biol Macromol ; 191: 646-656, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34582909

RESUMO

A lectin (designated as ARL) was purified first time from the Asparagus racemosus root with the molecular weight of 14.0 kDa containing about 4.8% carbohydrate. ARL showed hemagglutination activity in both mice and human erythrocytes that were inhibited by three complex sugars among the 26 sugars tested. ARL was thermostable that mostly preserved activity at its optimum pH 8.0. Around 48% and 52.5% human colorectal cancer (HCT-116) cells growth was inhibited by 160 µg/ml of ARL and 256 µg/ml of previously purified Geodorum densiflorum rhizome lectin (GDL). Induction of apoptosis in HCT-116 cells was confirmed by Hoechst 33342 staining, caspase inhibitors, but ROS generation was only observed for ARL. The expression level of BAX and p53 genes increased with a decrease of PARP gene expression for both lectins. The expression of FAS and FADD were increased with the decrease of WNT after treatment with GDL. ARL inhibited 68% and 26% of Ehrlich ascites carcinoma cell growth in vivo in mice after treating with 3.0 and 1.5 mg/kg/day doses for five consecutive days. ARL increased the expression level of NFκB and arrested S cell cycle phase in EAC cells, in contrast, G2/M phase was arrested by ARL and GDL in HCT-116.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Asparagus/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lectinas de Plantas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma de Ehrlich/tratamento farmacológico , Células HCT116 , Humanos , Masculino , Camundongos , NF-kappa B/metabolismo , PPAR gama/metabolismo , Lectinas de Plantas/química , Lectinas de Plantas/uso terapêutico , Proteína Supressora de Tumor p53/metabolismo
19.
J Cancer Res Clin Oncol ; 147(2): 445-457, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33205348

RESUMO

PURPOSE: Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFß and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. METHODS: Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. RESULTS: MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFß-SMAD, JAK-STAT, and Wnt-ßCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. CONCLUSIONS: Taken together, results from this study indicate that MASL decreases activity of JAK-STAT, TGFß-SMAD, and Wnt-ßCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Maackia/química , Neoplasias Bucais/tratamento farmacológico , Lectinas de Plantas/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Lectinas de Plantas/uso terapêutico , Fatores de Transcrição SOXB1/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transcrição Gênica/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
20.
Int J Biol Macromol ; 144: 509-526, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31857177

RESUMO

Lectins are (glyco)proteins capable of reversibly binding to specific carbohydrates, thus having various functions and applications. Plant lectins are the best studied, and the Leguminoseae family is highlighted in a number of published works, especially species of the Papilionoideae subfamily. Dalbergieae is one of the tribes in this subfamily comprising 49 genera and over 1300 species. From this tribe, about 26 lectins were studied, among which we can highlight the Arachis hypogaea lectin, widely used in cancer studies. Dalbergieae lectins demonstrate various carbohydrate specificities and biological activities including anti-inflammatory, vasorelaxant, nociceptive, antibacterial, antiviral among others. Structurally, these lectins are quite similar in their three-dimensional folding but present significant differences in oligomerization patterns and in the conservation of carbohydrate-recognition domain. Despite the existence of structural data from some lectins, only sparse literature has reported on this tribe's diversity, not to mention the range of biological effects, determined through specific assays. Therefore, this work will review the most important studies on Dalbergieae lectins and their potential biomedical applications.


Assuntos
Fabaceae/química , Lectinas de Plantas/química , Lectinas de Plantas/uso terapêutico , Sítios de Ligação , Carboidratos/química , Dobramento de Proteína , Homologia Estrutural de Proteína
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