PXD101 inhibits malignant progression and radioresistance of glioblastoma by upregulating GADD45A
Year: 2024
Type: article
Abstract: Histone deacetylase inhibitors (HDACis) have shown a significant antitumor effect in clinical studies, and PXD101 is a novel HDACi which can cross the blood-brain barrier. In this study, we showed that PXD101 could significantly inhibit the proliferation and invasion of glioblastoma (GBM) cells, while promoting their apoptosis and radiosensitivity. Furthermore, it was found that PXD101 exerted its antitumor function by upregulating the expression of the growth arrest and DNA damage inducible protein α (GADD45A). Mechanistically, PXD101 promoted the transcription of GADD45A by directly acetylating the histones H3 and H4, and GADD45A enhanced apoptosis and radiosensitivity through the activation of P38 in the GBM cells. In vivo experiments also showed that PXD101 combined with radiotherapy could significantly inhibit the growth of GBM. This study provides experimental evidence for application of the novel HDACi PXD101 in the treatment of GBM, as well as new molecular markers and potential intervention targets that may be used in preventing GBM malignant progression and radioresistance.
Authors: Xiaohong Hu, Peijun Zhou, Xingzhi Peng, Yiting Ouyang, Dan Li, Xia Wu, Lifang Yang
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Awards: G3832467648, G6612799435
OpenAlex ID: W4404542968