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1.
Biomed Pharmacother ; 161: 114462, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36933380

RESUMO

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of ß-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM.


Assuntos
Neoplasias Encefálicas , Furocumarinas , Glioblastoma , Animais , Camundongos , Humanos , Glioblastoma/patologia , Camundongos Nus , Proliferação de Células , Camundongos Endogâmicos C57BL , Transdução de Sinais , Furocumarinas/farmacologia , Furocumarinas/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Encefálicas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Biomed Pharmacother ; 153: 113416, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076484

RESUMO

Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo.


Assuntos
Benzofuranos , Neoplasias Encefálicas , Glioblastoma , Sirtuína 3 , Adulto , Animais , Apoptose , Benzofuranos/farmacologia , Benzofuranos/uso terapêutico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuína 3/metabolismo
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