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1.
Biochem Biophys Res Commun ; 671: 132-139, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37302286

RESUMO

Pancreatic cancer (PC) continues to be devastating due to its highly malignant nature and poor prognosis. The limited benefits of the chemotherapeutic drugs and increasing resistance pose a critical challenge to overcome and warrant investigations for new therapeutic agents. Several preclinical and clinical studies have suggested a possible role of the androgen receptor (AR) signaling pathway in PC development and progression. Nevertheless, the studies are limited and inconclusive in explaining the molecular link between AR signaling and PC. Selective androgen receptor modulators (SARMs) are small molecule drugs with high affinity for the androgen receptor. SARMs elicit selective anabolic activities while abrogating undesired androgenic side effects. There is no study focusing on the utility of SARMs as inhibitors of PC. Here, we report the first study evaluating the possible anti-carcinogenic influences of andarine, a member of the SARMs, on PC. The data we presented here has illustrated that andarine repressed PC cell growth and proliferation via cell cycle arrest at G0/G1 phase. Gene expression analysis revealed that it downregulates CDKN1A expression level accordingly. Furthermore, we established that the anti-carcinogenic activity of andarine is not mediated by the PI3K/AKT/mTOR signaling pathway, a crucial regulator of cell survival. Our findings suggest that andarine might be considered as a prospective drug for PC.


Assuntos
Anticarcinógenos , Receptores Androgênicos , Receptores Androgênicos/metabolismo , Anticarcinógenos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Androgênios/farmacologia , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Fase G1 , Linhagem Celular Tumoral
2.
Dev Dyn ; 251(12): 1914-1933, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35906989

RESUMO

The regenerative capacity varies significantly among the animal kingdom. Successful regeneration program in some animals results in the functional restoration of tissues and lost structures. Among the highly regenerative animals, axolotl provides multiple experimental advantages with its many extraordinary characteristics. It has been positioned as a regeneration model organism due to its exceptional renewal capacity, including the internal organs, central nervous system, and appendages, in a scar-free manner. In addition to this unique regeneration ability, the observed low cancer incidence, its resistance to carcinogens, and the reversing effect of its cell extract on neoplasms strongly suggest its usability in cancer research. Axolotl's longevity and efficient utilization of several anti-aging mechanisms underline its potential to be employed in aging studies.


Assuntos
Ambystoma mexicanum , Vertebrados , Animais , Ambystoma mexicanum/fisiologia , Envelhecimento/fisiologia
3.
Anticancer Agents Med Chem ; 22(2): 356-361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34238171

RESUMO

AIM: The study aimed to determine the cytotoxic and apoptotic effect of propofol on glioma cells. BACKGROUND: Propofol [2,6-diisopropylphenol] is a commonly used intravenous anesthetic. Propofol is known to have a mechanism of action on the PI3K-AKT pathway. OBJECTIVE: This study aimed to evaluate the effect of propofol on the proliferation and apoptosis of human glioma cells, as well as to investigate changes in expression levels of the PI3K-AKT signaling pathway genes. MATERIALS AND METHODS: The cytotoxic effect of propofol on the U-87 MG cell line was determined by WST-1 method. Annexin V-FITC and Mitoprobe JC-1 assay were used to measure apoptosis by flow cytometry. The expression levels of genes in the PI3K-AKT signaling pathway were investigated by qRT-PCR. RESULTS: We have shown that propofol induced apoptosis in U-87 MG cells by 17.1 fold compared to the untreated control. Furthermore, significant differences were found in the expression levels of the PI3K-AKT signaling pathway genes. CONCLUSION: As a result of our study, it was found that propofol caused differences in expression levels of PI3K-AKT signaling pathway genes and it was suggested that these differences may be related to apoptosis induction.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Propofol/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Fosfatidilinositol 3-Quinases/genética , Propofol/química , Propofol/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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