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1.
BMC Chem ; 17(1): 172, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017577

RESUMO

Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment.

2.
Oxid Med Cell Longev ; 2022: 1231970, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225175

RESUMO

Long-term exposure to high glucose leads to ß-cell dysfunction and death. Fibroblast growth factor 1 (FGF1) has emerged as a promising diabetes treatment, but its pharmaceutical role and mechanism against glucolipotoxicity-induced ß-cell dysfunction remain uncharacterized. Wild-type FGF1 (FGF1WT) may exhibit in vivo mitogenicity, but deletion of N-terminal residues 1-27 gives a nonmitogenic variant, ∆nFGF1, that does not promote cell proliferation and still retains the metabolic activity of FGF1WT. To investigate the roles of ∆nFGF1 on glucose regulation and potential islet ß-cell dysfunction, db/db mice were used as a model of type 2 diabetes. The results showed that insulin secretion and apoptosis of islet ß-cells were dramatically improved in ∆nFGF1-treated db/db mice. To further test the effects of ∆nFGF1 treatment, pancreatic ß-cell (MIN6) cells were exposed to a mixture of palmitic acid (PA) and high glucose (HG) to mimic glucolipotoxic conditions in vitro. Treatment with ∆nFGF1 significantly inhibited glucolipotoxicity-induced apoptosis. Mechanistically, ∆nFGF1 exerts a protective effect on ß-cells via activation of the AMPK/SIRT1/PGC-1α signaling pathway. These findings demonstrate that ∆nFGF1 protects pancreatic ß-cells against glucolipotoxicity-induced dysfunction and apoptosis.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose , Diabetes Mellitus Tipo 2/metabolismo , Fator 1 de Crescimento de Fibroblastos/metabolismo , Fator 1 de Crescimento de Fibroblastos/farmacologia , Glucose/metabolismo , Glucose/toxicidade , Células Secretoras de Insulina/metabolismo , Camundongos , Ácido Palmítico/metabolismo , Ácido Palmítico/toxicidade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo
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