Zn(II)-curc targets p53 in thyroid cancer cells

Alessia Garufi, Valerio D'Orazi, Alessandra Crispini, Gabriella D'Orazi

Research output: Contribution to journalArticle

Abstract

TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers.

Original languageEnglish
Pages (from-to)1241-1248
Number of pages8
JournalInternational Journal of Oncology
Volume47
Issue number4
DOIs
Publication statusPublished - Oct 1 2015

Fingerprint

Thyroid Neoplasms
Mutant Proteins
Neoplasms
Mutation
p53 Genes
Transcriptional Activation
Therapeutics
Down-Regulation
Phenotype
Gene Expression
Pharmaceutical Preparations
Genes

Keywords

  • Chemosensitivity
  • Mutant p53
  • P53 reactivation
  • Thyroid cancer
  • Zinc compound

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zn(II)-curc targets p53 in thyroid cancer cells. / Garufi, Alessia; D'Orazi, Valerio; Crispini, Alessandra; D'Orazi, Gabriella.

In: International Journal of Oncology, Vol. 47, No. 4, 01.10.2015, p. 1241-1248.

Research output: Contribution to journalArticle

Garufi, Alessia ; D'Orazi, Valerio ; Crispini, Alessandra ; D'Orazi, Gabriella. / Zn(II)-curc targets p53 in thyroid cancer cells. In: International Journal of Oncology. 2015 ; Vol. 47, No. 4. pp. 1241-1248.
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