title: Zn(II)-curc targets p53 in thyroid cancer cells.
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.
authors: Department of Experimental Oncology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Alessia
authors: A
authors: Garufi
authors: Department of Surgical Sciences, Sapienza University, Rome, Italy.
authors: Valerio
authors: V
authors: D'Orazi
authors: Department of Chemistry and Technologic Chemistry, University of Calabria, Cosenza, Italy.
authors: Alessandra
authors: A
authors: Crispini
authors: Department of Experimental Oncology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Gabriella
authors: G
authors: D'Orazi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D050505:Mutant Proteins / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D050505:Mutant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D017967:Zinc Compounds; D003474:Curcumin