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1.
Science ; 380(6649): eabn9257, 2023 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-37289866

RESUMEN

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.


Asunto(s)
Envejecimiento , Taurina , Animales , Humanos , Ratones , Envejecimiento/sangre , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Senescencia Celular , Haplorrinos , Longevidad/efectos de los fármacos , Longevidad/fisiología , Taurina/sangre , Taurina/deficiencia , Taurina/farmacología , Suplementos Dietéticos , Daño del ADN/efectos de los fármacos , Telomerasa/metabolismo
2.
Oncotarget ; 7(52): 86374-86387, 2016 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-27863439

RESUMEN

Malignant epithelial ovarian cancer (EOC) spheroids high frequently are detected in the malignant ascites of the patients with the extensive peritoneal metastasis of ovarian cancer, which represent a significant obstacle to efficacious treatment. Clinical data also suggested that EOC spheroids play a putative role in the development of chemoresistance. Since standard surgery and conventional chemotherapy is the only available treatment, there is an urgent need to identify a more effective therapeutic strategy. Recent studies demonstrated that curcumin exerts an anticancer effect in a variety of human cancers including ovarian cancer. This study evaluates anti-peritoneal metastasis and chemoresistance of curcumin related to the EOC spheroids. In this study, we confirm that the high invasive EOC cells forming the spheroids express a high level of a cancer stem cell (CSC) marker, aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which was significantly down-regulated by curcumin treatment. Curcumin treatment markedly enhances the sensitivity of EOC spheroids to cisplatin in a dose-dependent manner. Our experiments provided evidence that curcumin could abolish the sphere-forming capacity of EOC cells in a dose-dependent manner. Moreover, curcumin substantially suppressed the growth of the pre-existed EOC spheroids, inhibited the adhesion of EOC spheroids to ECM as well as the invasion of EOC spheroids to the mesothelial monolayers. We propose to re-purpose curcumin as anti-metastatic and chemoresistant agent for EOC management in combination with conventional regimen. Further preclinical studies are necessary to validate the anti-cancer effect of curcumin in patients with EOC.


Asunto(s)
Antineoplásicos/farmacología , Curcumina/farmacología , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Esferoides Celulares , Aldehído Deshidrogenasa/análisis , Familia de Aldehído Deshidrogenasa 1 , Carcinoma Epitelial de Ovario , Resistencia a Antineoplásicos , Femenino , Humanos , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Retinal-Deshidrogenasa
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