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1.
PLoS One ; 18(10): e0291905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37819868

RESUMO

Polyethylene glycol-23 glyceryl distearate (GDS-23), a diacylglycerol polyethylene glycol adduct, forms niosomes with a liposome-like structure and functions as an active ingredient in drug delivery systems. In addition, it upregulates antioxidant proteins such as heme oxygenase 1 and NAD(P)H-quinone dehydrogenase 1 in cells. However, the activation of nuclear factor E2-related factor-2 (Nrf2), which plays a role in inducing the expression of antioxidant proteins, and its protective effects induced by GDS-23 treatment against oxidative stress have not been elucidated. This study aimed at verifying the activation of Nrf2 by GDS-23 and clarifying its underlying mechanisms, and investigated whether GDS-23 protects against hydroquinone-induced cytotoxicity. Normal human epidermal keratinocytes were treated with GDS-23. Real-time reverse transcription-polymerase chain reaction, western blotting, and immunostaining were used to investigate the mechanism of Nrf2 activation, and neutral red assay was performed to evaluate cytotoxicity. GDS-23-treated cells showed an increase in antioxidant protein levels and stabilization of Nrf2 in the nucleus. During Nrf2 activation, p62, an autophagy-related adaptor protein, was phosphorylated at Ser349. Inhibition of the interaction between the phosphorylated p62 and Kelch-like ECH-associated protein 1 significantly suppressed the GDS-23-mediated induction of antioxidant protein expression. In addition, hydroquinone-induced cell toxicity was significantly attenuated by GDS-23. GDS-23 induced the intracellular antioxidant system by activating Nrf2 in a p62 phosphorylation-dependent manner without generating oxidative stress in the cells. GDS-23 may be applied as a multifunctional material for drug delivery system that enhances internal antioxidant systems.


Assuntos
Antioxidantes , Fator 2 Relacionado a NF-E2 , Humanos , Antioxidantes/metabolismo , Diglicerídeos/farmacologia , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Hidroquinonas/toxicidade , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Queratinócitos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Polietilenoglicóis/farmacologia , Polietilenoglicóis/metabolismo
2.
Bioorg Med Chem Lett ; 25(2): 172-4, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25522821

RESUMO

The first BNCT antitumor effects of BNNTs toward B16 melanoma cells were demonstrated. The use of DSPE-PEG2000 was effective for preparation of the BNNT-suspended aqueous solution. BNNT-DSPE-PEG2000 accumulated in B16 melanoma cells approximately three times higher than BSH and the higher BNCT antitumor effect was observed in the cells treated with BNNT-DSPE-PEG2000 compared to those treated with BSH, indicating that BNNT-DSPE-PEG2000 would be a possible candidate as a boron delivery vehicle for BNCT.


Assuntos
Antineoplásicos/administração & dosagem , Compostos de Boro/administração & dosagem , Terapia por Captura de Nêutron de Boro/métodos , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/radioterapia , Nanotubos , Animais , Antineoplásicos/química , Compostos de Boro/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Nanotubos/química , Nêutrons , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia
3.
Chem Commun (Camb) ; 50(82): 12325-8, 2014 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-25182569

RESUMO

closo-Dodecaborate-encapsulating liposomes were developed as boron delivery vehicles for neutron capture therapy. The use of spermidinium as a counter cation of closo-dodecaborates was essential not only for the preparation of high boron content liposome solutions but also for efficient boron delivery to tumors.


Assuntos
Antineoplásicos/administração & dosagem , Compostos de Boro/administração & dosagem , Animais , Antineoplásicos/química , Boro/administração & dosagem , Compostos de Boro/química , Terapia por Captura de Nêutron de Boro , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Lipossomos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Neoplasias/terapia , Carga Tumoral/efeitos dos fármacos
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