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1.
Int J Mol Sci ; 24(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36982678

RESUMO

Bisphenol A (BPA) promotes colon cancer by altering the physiological functions of hormones. Quercetin (Q) can regulate signaling pathways through hormone receptors, inhibiting cancer cells. The antiproliferative effects of Q and its fermented extract (FEQ, obtained by Q gastrointestinal digestion and in vitro colonic fermentation) were analyzed in HT-29 cells exposed to BPA. Polyphenols were quantified in FEQ by HPLC and their antioxidant capacity by DPPH and ORAC. Q and 3,4-dihydroxyphenylacetic acid (DOPAC) were quantified in FEQ. Q and FEQ exhibited antioxidant capacity. Cell viability with Q+BPA and FEQ+BPA was 60% and 50%, respectively; less than 20% of dead cells were associated with the necrosis process (LDH). Treatments with Q and Q+BPA induced cell cycle arrest in the G0/G1 phase, and FEQ and FEQ+BPA in the S phase. Compared with other treatments, Q positively modulated ESR2 and GPR30 genes. Using a gene microarray of the p53 pathway, Q, Q+BPA, FEQ and FEQ+BPA positively modulated genes involved in apoptosis and cell cycle arrest; bisphenol inhibited the expression of pro-apoptotic and cell cycle repressor genes. In silico analyses demonstrated the binding affinity of Q > BPA > DOPAC molecules for ERα and ERß. Further studies are needed to understand the role of disruptors in colon cancer.


Assuntos
Neoplasias do Colo , Quercetina , Humanos , Quercetina/farmacologia , Proliferação de Células , Antioxidantes/farmacologia , Células HT29 , Ácido 3,4-Di-Hidroxifenilacético/farmacologia , Neoplasias do Colo/tratamento farmacológico , Compostos Benzidrílicos/farmacologia
2.
Curr Pharm Biotechnol ; 24(13): 1682-1693, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36872365

RESUMO

BACKGROUND: The need to combat and reduce the incidence, virulence, and drug resistance of species belonging to Candida genus, has led to the development of new strategies. Nanotechnology, through the implementation of nanomaterials, has emerged as an infallible tool to treat various diseases caused by pathogens, where its mechanisms of action prevent the development of undesirable pharmacological resistance. OBJECTIVE: The antifungal activity and adjuvant properties of biogenic silver nanoparticles in different Candida species (C. parapsilosis, C. glabrata, and C. albicans) are evaluated. METHODS: The biogenic metallic nanoparticles were developed by quercetin-mediated biological synthesis. The physicochemical properties were studied by light scattering, electrophoretic mobility, UV-vis and infrared spectroscopy, and transmission electron microscopy. The elucidation of mechanisms of antifungal action was carried out under stress conditions in Candida species at the cell wall and response to oxidative stress. RESULTS: Small silver nanoparticles (≈ 16.18 nm) with irregular morphology, and negative surface electrical charge (≈ -48.99 mV), were obtained through quercetin-mediated biosynthesis. Infrared spectra showed that the surface of silver nanoparticles is functionalized with the quercetin molecule. The antifungal activity of biogenic nanoparticles had efficacy in the following trend C. glabrata ≥ C. parapsilosis > C. albicans. Biogenic nanoparticles and stressors showed synergistic and potentiated antifungal effects through cell damage, osmotic stress, cell wall damage, and oxidative stress. CONCLUSIONS: Silver nanoparticles synthesized by quercetin-mediated biosynthesis could be implemented as a powerful adjuvant agent to enhance the inhibition effects of diverse compounds over different Candida species.


Assuntos
Candida , Nanopartículas Metálicas , Antifúngicos/farmacologia , Antifúngicos/química , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Pressão Osmótica , Quercetina/farmacologia , Candida albicans , Estresse Oxidativo , Parede Celular , Testes de Sensibilidade Microbiana
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