β-elemene promotes the senescence of glioma cells through regulating YAP-CDK6 signaling

Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. beta-elemene, which is a bioactive compound extracted from a Chinese herb, Curcuma wenyujin, has been reported to reduce resistance of chemotherapeutic drugs and induce apoptosis in tumor cells. However, the role and mechanisms of beta-elemene in glioma senescence remains unknown. In the present study, we found that a low concentration of beta-elemene (10 mu g/mL) induced senescence in glioma cells, including reduction of cell proliferation, hypertrophic morphology, increase of senescence-associated beta-galactosidase (SA-beta-Gal) activity, upregulation of several senescence-associated genes such as p16, p53 and NF-kappa B, and downregulation of Lamin B1. However, a high concentration of beta-elemene induced apoptosis in glioma cells. Treatment with beta-elemene caused a marked down-regulation of Yes-associated protein (YAP) expression in glioma cells, which is a key transcriptional co-activator in multiple cancers. Moreover, cyclin dependent kinase 6 (CDK6), which is a known downstream target of YAP, was decreased in glioma cells that treated with beta-elemene. The overexpression of YAP and CDK6 significantly rescued beta-elemene-induced senescence in glioma cells. Finally, beta-elemene treatment also induced the senescence of glioma cells in glioma xenograft model through inactivation of YAP-CDK6 pathways, which might inhibit the glioma growth. Taken together, these results reveal a previously unknown role of beta-elemene in glioma cell senescence in vitro and in vivo that is associated with YAP-CDK6 signaling pathway, which will enhance our understanding of glioma cell senescence, and provide novel strategies for the treatment of gliomas.

Automated summary

The study found that low concentration of beta-elemene induces senescence in glioma cells, while high concentration leads to apoptosis, through modulation of the YAP-CDK6 signaling pathway. Overexpression of YAP and CDK6 significantly rescues beta-elemene-induced senescence in glioma cells, providing a potential novel therapeutic strategy for gliomas.