https://scholars.lib.ntu.edu.tw/handle/123456789/627262
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Loo, Ser Yue | en_US |
dc.contributor.author | Syn, Nicholas L. | en_US |
dc.contributor.author | Koh, Angele Pei Fern | en_US |
dc.contributor.author | Teng, Janet Cheng Fei | en_US |
dc.contributor.author | Deivasigamani, Amudha | en_US |
dc.contributor.author | Tan, Tuan Zea | en_US |
dc.contributor.author | Thike, Aye Aye | en_US |
dc.contributor.author | Vali, Shireen | en_US |
dc.contributor.author | Kapoor, Shweta | en_US |
dc.contributor.author | Wang, Xiaoyuan | en_US |
dc.contributor.author | Wang, Jiong Wei | en_US |
dc.contributor.author | Tan, Puay Hoon | en_US |
dc.contributor.author | Yip, George W. | en_US |
dc.contributor.author | Sethi, Gautam | en_US |
dc.contributor.author | RUBY YUN-JU HUANG | en_US |
dc.contributor.author | Hui, Kam Man | en_US |
dc.contributor.author | Wang, Lingzhi | en_US |
dc.contributor.author | Goh, Boon Cher | en_US |
dc.contributor.author | Kumar, Alan Prem | en_US |
dc.date.accessioned | 2023-01-16T02:56:07Z | - |
dc.date.available | 2023-01-16T02:56:07Z | - |
dc.date.issued | 2021-12-01 | - |
dc.identifier.issn | 2058-7716 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/627262 | - |
dc.description.abstract | Clinical trials repurposing peroxisome proliferator-activated receptor-gamma (PPARγ) agonists as anticancer agents have exhibited lackluster efficacy across a variety of tumor types. Here, we report that increased PPARG expression is associated with a better prognosis but is anticorrelated with histone deacetylase (HDAC) 1 and 2 expressions. We show that HDAC overexpression blunts anti-proliferative and anti-angiogenic responses to PPARγ agonists via transcriptional and post-translational mechanisms, however, these can be neutralized with clinically approved and experimental HDAC inhibitors. Supporting this notion, concomitant treatment with HDAC inhibitors was required to license the tumor-suppressive effects of PPARγ agonists in triple-negative and endocrine-refractory breast cancer cells, and combination therapy also restrained angiogenesis in a tube formation assay. This combination was also synergistic in estrogen receptor-alpha (ERα)–positive cells because HDAC blockade abrogated ERα interference with PPARγ-regulated transcription. Following a pharmacokinetics optimization study, the combination of rosiglitazone and a potent pan-HDAC inhibitor, LBH589, stalled disease progression in a mouse model of triple-negative breast cancer greater than either of the monotherapies, while exhibiting a favorable safety profile. Our findings account for historical observations of de-novo resistance to PPARγ agonist monotherapy and propound a therapeutically cogent intervention against two aggressive breast cancer subtypes. | en_US |
dc.language.iso | en | en_US |
dc.publisher | SPRINGERNATURE | en_US |
dc.relation.ispartof | Cell Death Discovery | en_US |
dc.subject | MANGANESE SUPEROXIDE-DISMUTASE; LIGAND TROGLITAZONE; MULTIPLE-MYELOMA; COLON-CANCER; PHASE-II; IN-VITRO; THERAPY; RECEPTOR; EXPRESSION; CARCINOMA | en_US |
dc.title | Epigenetic derepression converts PPARγ into a druggable target in triple-negative and endocrine-resistant breast cancers | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1038/s41420-021-00635-5 | - |
dc.identifier.pmid | 34580286 | - |
dc.identifier.scopus | 2-s2.0-85115775359 | - |
dc.identifier.isi | WOS:000700398400001 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/85115775359 | - |
dc.relation.journalvolume | 7 | en_US |
dc.relation.journalissue | 1 | en_US |
item.fulltext | no fulltext | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
item.openairetype | journal article | - |
item.languageiso639-1 | en | - |
crisitem.author.dept | School of Medicine | - |
crisitem.author.dept | Master's Program in Smart Medicine and Health Informatics (SMARTMHI) | - |
crisitem.author.orcid | 0000-0001-6376-3185 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | International College | - |
顯示於: | 醫學系 |
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