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Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors
Chen, Geer; Zhu, Xiaoyu; Li, Jiaqi; Zhang, Yao; Wang, Xiaoxuan; Zhang, Ren; Qin, Xinchen; Chen, Xi; Wang, Junyi; Liao, Weilin; Wu, Zongjin; Lu, Lu; Wu, Weiyu; Yu, Haijie; Ma, Lijuan
2022-10-03
Source PublicationPharmacological Research
ISSN1043-6618
Volume185
Abstract

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

KeywordAcetylation Anacardic ACid (Pubchem Cid: 167551) C646 (Pubchem Cid: 1285941) Celastrol Celastrol (Pubchem Cid: 122724) Ci994 (Pubchem Cid: 2746) Hdac Histone Modification Lung Cancer Mc1568 (Pubchem Cid: 71311876) Ms275 (Pubchem Cid: 4261) Nu9056 (Pubchem Cid: 72201043) Saha (Pubchem Cid: 5311)
DOI10.1016/j.phrs.2022.106487
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000878743900003
PublisherACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
Scopus ID2-s2.0-85139867393
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorYu, Haijie; Ma, Lijuan
AffiliationDr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China
First Author AffilicationUniversity of Macau
Corresponding Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Chen, Geer,Zhu, Xiaoyu,Li, Jiaqi,et al. Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors[J]. Pharmacological Research, 2022, 185.
APA Chen, Geer., Zhu, Xiaoyu., Li, Jiaqi., Zhang, Yao., Wang, Xiaoxuan., Zhang, Ren., Qin, Xinchen., Chen, Xi., Wang, Junyi., Liao, Weilin., Wu, Zongjin., Lu, Lu., Wu, Weiyu., Yu, Haijie., & Ma, Lijuan (2022). Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors. Pharmacological Research, 185.
MLA Chen, Geer,et al."Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors".Pharmacological Research 185(2022).
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