D-galactose induces senescence of glioblastoma cells through YAP-CDK6 pathway

Area of Science:

• Oncology
• Cell Biology
• Aging Research

Background:

• Glioblastoma treatment with radiotherapy and chemotherapy can lead to cellular senescence, but the underlying molecular mechanisms are not fully understood.
• Cellular senescence plays a complex role in cancer progression and treatment response.

Purpose of the Study:

• To investigate the potential of D-galactose (D-gal), a reducing sugar, to induce senescence in glioblastoma cells.
• To elucidate the molecular pathways involved in D-gal-induced glioblastoma senescence.
• To establish a novel model for studying glioblastoma senescence.

Main Methods:

• Treatment of glioblastoma cell lines (C6 and U87MG) with D-galactose.
• Assessment of senescence characteristics: cell proliferation, morphology, senescence-associated β-galactosidase activity, Lamin B1 expression, and senescence-associated gene expression (p16, p53, NF-κB).
• Investigation of the YAP-CDK6 signaling pathway and the effect of metformin on D-gal-induced senescence.

Main Results:

• D-galactose induced typical senescence characteristics in glioblastoma cells, including reduced proliferation and altered gene expression.
• D-galactose was more effective in inducing senescence than etoposide.
• D-galactose inactivated the YAP-CDK6 signaling pathway; YAP or CDK6 overexpression restored senescence.
• Metformin, an anti-aging agent, activated YAP-CDK6 and inhibited D-gal-induced senescence.

Conclusions:

• D-galactose serves as an effective inducer of senescence in glioblastoma cells.
• The YAP-CDK6 signaling pathway is a key mediator of D-gal-induced glioblastoma senescence.
• This study provides a new model for glioblastoma senescence analysis and suggests potential therapeutic strategies targeting the YAP-CDK6 pathway.