Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors

• DOI: 10.1016/j.phrs.2022.106487
• Publication Date: 2022-10-03T15:46:08Z
• Authors: Geer Chen; Xiaoyu Zhu; Jiaqi Li; Yao Zhang; Xiaoxuan Wang; Ren Zhang; Xinchen Qin; Xi Chen; Junyi Wang; Weilin Liao; Zongjin Wu; Lu Lu; Weiyu Wu; Haijie Yu; Lijuan Ma
• Keywords: Celastrol; Histone acetyltransferase; HDAC11; Trichostatin A; Histone deacetylase 5

Alterations in histone modification have been linked to cancer development and progression. Celastrol, a Chinese herbal compound, shows potent anti-tumor effects through multiple signaling pathways. However, the involvement of modifications this process has not yet illustrated. In study, barcode sequencing eukaryotic genome-wide deletion library revealed that modifications, especially acetylation associated with NuA4 acetyltransferase complex, were involved anti-proliferation actions celastrol. The essential roles verified by celastrol sensitivity tests cells lacking specific genes, such as genes encoding subunits Swr1 complex. combination deacetylase inhibitors (HDACi), rather than inhibitors, synergistically suppressed cell proliferation. addition upregulating H4K16 (H4K16ac), regulates H3K4 tri-methylation H3S10 phosphorylation. Celastrol treatment significantly enhanced suppressive HDACi on lung allografts mice, significant H4K16ac upregulation, indicating is potential novel therapeutic approach for patients cancer.