Journal article
The Synthetic Curcumin Analog HO-3867 Rescues Suppression of PLAC1 Expression in Ovarian Cancer Cells
Pharmaceuticals (Basel, Switzerland), Vol.14(9), p.942
09/01/2021
DOI: 10.3390/ph14090942
PMCID: PMC8465575
PMID: 34577642
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 TP53 mutations. Ovarian cancer cells OVCAR3 and ES-2, both harboring TP53 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.
Details
- Title: Subtitle
- The Synthetic Curcumin Analog HO-3867 Rescues Suppression of PLAC1 Expression in Ovarian Cancer Cells
- Creators
- Eric J. Devor - Roy J. and Lucille A. Carver College of MedicineBrandon M. Schickling - University of IowaJace R. Lapierre - Roy J. and Lucille A. Carver College of MedicineDavid P. Bender - Roy J. and Lucille A. Carver College of MedicineJesus Gonzalez-Bosquet - Roy J. and Lucille A. Carver College of MedicineKimberly K. Leslie - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Pharmaceuticals (Basel, Switzerland), Vol.14(9), p.942
- DOI
- 10.3390/ph14090942
- PMID
- 34577642
- PMCID
- PMC8465575
- NLM abbreviation
- Pharmaceuticals (Basel)
- ISSN
- 1424-8247
- eISSN
- 1424-8247
- Publisher
- Mdpi
- Number of pages
- 11
- Grant note
- 2018 ABOG/AAOGF Bridge Funding Award R01CA99908; R01CA184101 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of Iowa Department of Obstetrics and Gynecology Research Development Fund Iowa cancer patient advocacy group CCKMA P30CA086862 / Genome Core Facility of the Iowa Institute of Human Genetics through NIH/NCI
- Language
- English
- Date published
- 09/01/2021
- Academic Unit
- Orthopedics and Rehabilitation; Obstetrics and Gynecology
- Record Identifier
- 9984315571902771
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