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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Devor, EJ; Schickling, BM; Lapierre, JR; Bender, DP; Gonzalez-Bosquet, J; Leslie, KK

Published Date

  • September 21, 2021

Published In

Volume / Issue

  • 14 / 9

PubMed ID

  • 34577642

Pubmed Central ID

  • PMC8465575

International Standard Serial Number (ISSN)

  • 1424-8247

Digital Object Identifier (DOI)

  • 10.3390/ph14090942

Language

  • eng

Conference Location

  • Switzerland