Curcumin stabilizes p53 by interaction with NAD(P)H:quinone oxidoreductase 1 in tumor-derived cell lines

Publication date: Available online 9 September 2019Source: Redox BiologyAuthor(s): Carlos César Patiño-Morales, Ernesto Soto-Reyes, Elena Arechaga-Ocampo, Elizabeth Ortiz-Sánchez, Verónica Antonio-Véjar, José Pedraza-Chaverri, Alejandro García-CarrancáAbstractCurcumin is a natural phytochemical with potent anti-neoplastic properties including modulation of p53. Targeting p53 activity has been suggested as an important strategy in cancer therapy. The purpose of this study was to describe a mechanism by which curcumin restores p53 levels in human cancer cell lines.HeLa, SiHa, CaSki and MDA-MB-231 cells were exposed to curcumin and a pulse and chase and immunoprecipitation assays were performed. Here we showed that curcumin increases the half-life of p53 by a physical interaction between p53-NQO1 (p53 - NAD(P)H:quinone oxidoreductase 1) proteins after treatment with curcumin. Interestingly, the cell viability assay after treatment with curcumin showed that the cytotoxic activity was selectively higher in cervical cancer cells contained wild type p53 but not in breast cancer cells contained mutated p53. The cytotoxic effect of curcumin in cervical cancer cells was related to the complex p53-NQO1 that avoids the interaction between p53 and its negative regulator ubiquitin ligase E6-associated protein (E6AP). Finally, we demonstrated that in pancreatic epithelioid carcinoma cells (PANC1) that are knockout for NQO1, the reestablishment of NQO1 expression can stabilize p53 ...
Source: Redox Biology - Category: Biology Source Type: research