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1.
Int J Biol Macromol ; 166: 1173-1187, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33159939

RESUMO

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.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma de Ehrlich/patologia , Caspases/metabolismo , Lectinas/uso terapêutico , Sistema de Sinalização das MAP Quinases , Musa/química , Neovascularização Patológica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Aglutinação/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/metabolismo , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Lectinas/isolamento & purificação , Lectinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/metabolismo , Fosforilação/efeitos dos fármacos , Testes de Toxicidade Aguda
2.
J Biol Inorg Chem ; 24(7): 1115-1126, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31538255

RESUMO

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.


Assuntos
Indutores da Angiogênese/metabolismo , Indutores da Angiogênese/farmacologia , Clitoria/química , Flores/química , Nanopartículas Metálicas , Prata/metabolismo , Prata/farmacologia , Indutores da Angiogênese/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Células MCF-7 , Extratos Vegetais/metabolismo , Prata/química
3.
Nutr Cancer ; 71(2): 285-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30596280

RESUMO

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.


Assuntos
Inibidores da Angiogênese/farmacologia , Carcinoma de Ehrlich/irrigação sanguínea , Carcinoma de Ehrlich/tratamento farmacológico , Lectinas/farmacologia , Musa/química , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Aglutininas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Extratos Vegetais/farmacologia , Fatores de Crescimento do Endotélio Vascular/metabolismo
4.
Biomed Pharmacother ; 96: 1299-1309, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29174033

RESUMO

Praecitrullus fistulosus, belonging to the family of Cucurbitaceae is a tropical vegetable and medicinal plant, grown and consumed extensively in subtropical countries, including the subcontinent India. However, there are limited reports on the medicinal properties of the plant and need to be explored. The lectin identified from the fruit sap of Praecitrullus fistulosus, named as PfLP, possesses potent agglutinating activity against trypsinized rabbit erythrocytes and exhibited its functional role against tumor progression, on in vitro &in vivo models. Experimental results revealed that PfLP shows a promising cytotoxic effect against multiple cancer cell lines. Further, we examined the in vivo anticancer and anti-angiogenic properties of PfLP against EAC bearing mice. PfLP treatment resulted in tumor growth inhibition and increased the life-span of the EAC bearing mice, without showing any detectable side effects, as revealed by histological parameters. Further, a significant decrease in the ascites VEGF secretion level was parallel with a drastic reduction in tumoral neovasculature as evidence for angiogenic parameters. Gelatin zymogram study reveals that PfLP inhibits metalloproteinases (MMP-2 & MMP-9) activity in order to execute its anti-angiogenic effect. PfLP has also inducing apoptosis, in cancer cells was revealed by DNA fragmentation assay followed by Giemsa and AO/EBr staining method, showed the apoptotic bodies and condensed nuclei compared to control cells. More interestingly, PfLP did not exhibit any adverse side effects or secondary complications in normal mice. These results clearly exhibit the potential role of PfLP in regressing the tumor progression by targeting angiogenesis and inducing cell death in mouse transplantable tumor.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Cucurbitaceae/química , Frutas/química , Lectinas/farmacologia , Neoplasias/tratamento farmacológico , Plantas Medicinais/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HT29 , Células HeLa , Humanos , Células K562 , Células MCF-7 , Metaloproteases/metabolismo , Camundongos , Neoplasias/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Extratos Vegetais/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
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