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

ABSTRACT: Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. ?-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 ?-elemene in glioma senescence remains unknown. In the present study, we found that a low concentration of ?-elemene (10 ?g/mL) induced senescence in glioma cells, including reduction of cell proliferation, hypertrophic morphology, increase of senescence-associated ?-galactosidase (SA-?-Gal) activity, upregulation of several senescence-associated genes such as p16, p53 and NF-?B, and downregulation of Lamin B1. However, a high concentration of ?-elemene induced apoptosis in glioma cells. Treatment with ?-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 ?-elemene. The overexpression of YAP and CDK6 significantly rescued ?-elemene-induced senescence in glioma cells. Finally, ?-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 ?-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.

SUBMITTER: Yang D 

PROVIDER: S-EPMC7868755 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature