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The Synthetic Curcumin Analog HO-3867 Rescues Suppression of PLAC1 Expression in Ovarian Cancer Cells.

dc.contributor.author Devor, Eric J
dc.contributor.author Schickling, Brandon M
dc.contributor.author Lapierre, Jace R
dc.contributor.author Bender, David P
dc.contributor.author Gonzalez-Bosquet, Jesus
dc.contributor.author Leslie, Kimberly K
dc.date.accessioned 2021-10-13T16:22:51Z
dc.date.available 2021-10-13T16:22:51Z
dc.date.issued 2021-09-21
dc.identifier ph14090942
dc.identifier.issn 1424-8247
dc.identifier.issn 1424-8247
dc.identifier.uri https://hdl.handle.net/10161/23920
dc.description.abstract Elevated expression of placenta-specific protein 1 (PLAC1) is associated with the increased proliferation and invasiveness of a variety of human cancers, including ovarian cancer. Recent studies have shown that the tumor suppressor p53 directly suppresses PLAC1 transcription. However, mutations in p53 lead to the loss of PLAC1 transcriptional suppression. Small molecules that structurally convert mutant p53 proteins to wild-type conformations are emerging. Our objective was to determine whether the restoration of the wild-type function of mutated p53 could rescue PLAC1 transcriptional suppression in tumors harboring certain <i>TP53</i> mutations. Ovarian cancer cells OVCAR3 and ES-2, both harboring <i>TP53</i> missense mutations, were treated with the p53 reactivator HO-3867. Treatment with HO-3867 successfully rescued PLAC1 transcriptional suppression. In addition, cell proliferation was inhibited and cell death through apoptosis was increased in both cell lines. We conclude that the use of HO-3867 as an adjuvant to conventional therapeutics in ovarian cancers harboring TP53 missense mutations could improve patient outcomes. Validation of this conclusion must, however, come from an appropriately designed clinical trial.
dc.language eng
dc.publisher MDPI AG
dc.relation.ispartof Pharmaceuticals (Basel, Switzerland)
dc.relation.isversionof 10.3390/ph14090942
dc.subject ES-2
dc.subject HO-3867
dc.subject OVCAR3
dc.subject ovarian cancer
dc.subject p53
dc.subject placenta-specific protein 1 (PLAC1)
dc.subject reactivator
dc.subject steric hindrance
dc.title The Synthetic Curcumin Analog HO-3867 Rescues Suppression of PLAC1 Expression in Ovarian Cancer Cells.
dc.type Journal article
duke.contributor.id Schickling, Brandon M|0722989
dc.date.updated 2021-10-13T16:22:49Z
pubs.begin-page 942
pubs.end-page 942
pubs.issue 9
pubs.organisational-group School of Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Duke
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 14
duke.contributor.orcid Schickling, Brandon M|0000-0002-2312-268X


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