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D-galactose induces senescence of glioblastoma cells through YAP-CDK6 pathway.
Xu, Xingxing; Shen, Xiya; Feng, Wenjin; Yang, Danlu; Jin, Lingting; Wang, Jiaojiao; Wang, Mianxian; Ting, Zhang; Xue, Feng; Zhang, Jingjing; Meng, Chaobo; Chen, Roumeng; Zheng, Xinru; Du, Leilei; Xuan, Lina; Wang, Ying; Xie, Tian; Huang, Zhihui.
Afiliación
  • Xu X; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Shen X; Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, and Department of Neurosurgery of Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, China.
  • Feng W; Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Yang D; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Jin L; Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, and Department of Neurosurgery of Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, China.
  • Wang J; Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Wang M; Zhejiang Sinogen Medical Equipment Co., Ltd, Wenzhou, 325000, Zhejiang, China.
  • Ting Z; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Xue F; Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, and Department of Neurosurgery of Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, China.
  • Zhang J; Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Meng C; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Chen R; Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, and Department of Neurosurgery of Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, China.
  • Zheng X; Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Du L; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Xuan L; Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, and Department of Neurosurgery of Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, China.
  • Wang Y; Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Xie T; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • Huang Z; Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, and Department of Neurosurgery of Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, China.
Aging (Albany NY) ; 12(18): 18501-18521, 2020 Sep 29.
Article en En | MEDLINE | ID: mdl-32991321
ABSTRACT
Treatment of glioblastoma using radiotherapy and chemotherapy has various outcomes, key among them being cellular senescence. However, the molecular mechanisms of this process remain unclear. In the present study, we tested the ability of D-galactose (D-gal), a reducing sugar, to induce senescence in glioblastoma cells. Following pretreatment with D-gal, glioblastoma cell lines (C6 and U87MG) showed typical characteristics of senescence. These included the reduced cell proliferation, hypertrophic morphology, increased senescence-associated ß-galactosidase activity, downregulation of Lamin B1, and upregulation of several senescence-associated genes such as p16, p53, and NF-κB. Furthermore, our results showed that D-gal was more suitable than etoposide (a DNA-damage drug) in inducing senescence of glioblastoma cells. Mechanistically, D-gal inactivated the YAP-CDK6 signaling pathway, while overexpression of YAP or CDK6 could restore D-gal-induced senescence of C6 cells. Finally, metformin, an anti-aging agent, activated the YAP-CDK6 pathway and suppressed D-gal-induced senescence of C6 cells. Taken together, these findings established a new model for analyzing senescence in glioblastoma cells, which occurred through the YAP-CDK6 pathway. This is expected to provide a basis for development of novel therapies for the treatment of glioblastoma.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2020 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2020 Tipo del documento: Article País de afiliación: China