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1.
Int J Biol Macromol ; 166: 1173-1187, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33159939

RESUMEN

In the present study aimed to purify the lectin from the sap of Musa acuminata pseudostem and elucidate the apoptotic and angiogenic molecular mechanism in both in-vitro and in-vivo model. Mannose specific lectin was purified by using mannose affinity column chromatography and analyzed by RP-HPLC, SDS-PAGE, and PAS staining method. Furthermore, the protein was identified by MALDI-MS/MS. MAL effectively agglutinates trypsinized RBCs and showed effective cytotoxicity against various human cancer cell lines. MAL mitigates the cell proliferation, colony formation, cell migration, arrest the cell cycle in the G2/M phase, and induce apoptosis by altering the expression of apoptotic proteins/mRNA level (Bax and Bcl-2) via caspase 8/9, 3 dependent pathway in both in-vitro and in-vivo. Supporting this, in-vivo EAC tumor mice models prove the efficacy of MAL by inducing cell death and inhibiting the neovessel formation by targeting the MVD, inhibition of VEGF secretion, suppressing the expression of MMPs, HIF-1α, Flt-1, Akt, Jnk, and Erk1/2. More importantly, the MAL treatment leads to effective inhibition of tumor growth and an increase in the survivability of EAC mice. Our study summarizes that the MAL having a significant anticancer potential expressively degenerates the tumor development by inducing apoptosis and suppressing neoangiogenesis.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma de Ehrlich/patología , Caspasas/metabolismo , Lectinas/uso terapéutico , Sistema de Señalización de MAP Quinasas , Musa/química , Neovascularización Patológica/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Aglutinación/efectos de los fármacos , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Células Sanguíneas/efectos de los fármacos , Células Sanguíneas/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Pollos , Membrana Corioalantoides/efectos de los fármacos , Membrana Corioalantoides/metabolismo , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Femenino , Células HeLa , Humanos , Lectinas/aislamiento & purificación , Lectinas/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos BALB C , Proteínas de Neoplasias/metabolismo , Fosforilación/efectos de los fármacos , Pruebas de Toxicidad Aguda
2.
J Biol Inorg Chem ; 24(7): 1115-1126, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31538255

RESUMEN

Biosynthesis of silver nanoparticles (CTNP's) by Clitoria ternatea flower in the aqueous extract was investigated. Synthesized nanoparticles were characterized by using UV-Visible spectroscopy, followed by DLS, Zeta potential, XRD, FTIR, SEM, and AFM. The biocompatibility nature of CTNP's was determined using erythrocytes model system. Cytotoxicity of CTNP's against MCF-7 and EAC cells were determined by using MTT and Trypan blue exclusion method and their IC50 was found to be 19.37 µg/mL and 24 µg/mL. Cytotoxic potential of CTNP's was further confirmed by clonogenic assay. Further in vivo studies using EAC mice model supports the anti-cancer potential of silver nanoparticles. Results found that the CTNP's effectively control the proliferation rate by inhibiting the ascites secretion and cellular density. Further quantification of VEGF, microvessel density counts and CAM assays show the anti-angiogenic potential of the CTNP's. The apoptotic inducing activity of CTNP's was confirmed by DNA fragmentation, fluorescent staining studies. More interestingly, EAC treated mice exhibit significant increase in lifespan (~ 2.25 fold) compared to control EAC mice. Interestingly CTNP's did not exhibit any secondary complications against normal mice. The present findings give an experimental proof that the CTNP's could serve as a promising candidate to overcome limitations of existing conventional cancer therapeutics.


Asunto(s)
Inductores de la Angiogénesis/metabolismo , Inductores de la Angiogénesis/farmacología , Clitoria/química , Flores/química , Nanopartículas del Metal , Plata/metabolismo , Plata/farmacología , Inductores de la Angiogénesis/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Humanos , Células MCF-7 , Extractos Vegetales/metabolismo , Plata/química
3.
Nutr Cancer ; 71(2): 285-300, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30596280

RESUMEN

Lifestyle and nutritional changes have contributed much to the somatic genetic changes which have concurrently led to an increase cancer in humans. Hence the plant-based and nutritional involvements block oncogenic transformation are in good demand. We evaluate Phloem exudates of the dietary plant, Musa acuminate pseudostem, the initial domesticated plant species with the effective lectin activity for its functional role against the tumor development and its mechanism of action. Our experimental data exhibit that Musa acuminata Lectin Protein (MALP) shows a promising cytotoxic effect against the various human cancer cell lines. Supporting this, we evaluate the in vivo anti-tumor and anti-angiogenic activity of MALP in Ehrlich Ascites Carcinoma mice model (EAC). MALP treatment resulted in tumor growth inhibition and increased the lifespan of the EAC-bearing mice without showing any side effects on normal mice, as revealed by histological parameters. Further, a significant decrease in the ascites vascular endothelial growth factor (VEGF) secretion and microvessel density supports the anti-angiogenic property of the MALP. Apoptosis-inducing activity of MALP was revealed by DNA fragmentation assay, Caspase-3 inhibitor assay and cellular morphology were studied by fluorescence staining methods. Our study delivers the real evidence that MALP with a promising an anticancer potential expressively degenerates the tumor development by affecting angiogenesis and apoptosis.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Carcinoma de Ehrlich/irrigación sanguínea , Carcinoma de Ehrlich/tratamiento farmacológico , Lectinas/farmacología , Musa/química , Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Aglutininas/farmacología , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Ehrlich/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Humanos , Técnicas In Vitro , Ratones , Ratones Endogámicos BALB C , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Extractos Vegetales/farmacología , Factores de Crecimiento Endotelial Vascular/metabolismo
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