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

Carlos César Patiño-Morales, Ernesto Soto Reyes, Elena Aréchaga, Elizabeth Ortiz-Sánchez, Verónica Antonio-Véjar, José Pedraza-Chaverri, Alejandro M García Carrancá

Research output: Contribution to journalArticle

Abstract

Curcumin 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 in presence of curcumin. Collectively, our findings showed that curcumin is necessary to promote the protein interaction of NQO1 with p53, therefore, it increases the half-life of p53, and permits the cytotoxic effect of curcumin in cancer cells containing wild type p53. Our findings suggest that the use of curcumin may reactivate the p53 pathway in cancer cells with p53 wild-type.

Original languageEnglish (US)
Article number101320
JournalRedox Biology
Volume28
DOIs
StatePublished - Jan 1 2020

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Curcumin
Tumor Cell Line
NAD
Tumors
Oxidoreductases
Cells
Uterine Cervical Neoplasms
Half-Life
Assays
Neoplasms
benzoquinone
Epithelioid Cells
Proteins
Phytochemicals
Ligases
Ubiquitin
Immunoprecipitation
Cell Survival
Modulation
Breast Neoplasms

Keywords

  • Curcumin
  • E6AP
  • NQO1
  • P53
  • Tumour cell lines

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

Cite this

Curcumin stabilizes p53 by interaction with NAD(P)H:quinone oxidoreductase 1 in tumor-derived cell lines. / Patiño-Morales, Carlos César; Soto Reyes, Ernesto; Aréchaga, Elena; Ortiz-Sánchez, Elizabeth; Antonio-Véjar, Verónica; Pedraza-Chaverri, José; García Carrancá, Alejandro M.

In: Redox Biology, Vol. 28, 101320, 01.01.2020.

Research output: Contribution to journalArticle

Patiño-Morales, Carlos César ; Soto Reyes, Ernesto ; Aréchaga, Elena ; Ortiz-Sánchez, Elizabeth ; Antonio-Véjar, Verónica ; Pedraza-Chaverri, José ; García Carrancá, Alejandro M. / Curcumin stabilizes p53 by interaction with NAD(P)H:quinone oxidoreductase 1 in tumor-derived cell lines. In: Redox Biology. 2020 ; Vol. 28.
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AU - Ortiz-Sánchez, Elizabeth

AU - Antonio-Véjar, Verónica

AU - Pedraza-Chaverri, José

AU - García Carrancá, Alejandro M

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AB - Curcumin 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 in presence of curcumin. Collectively, our findings showed that curcumin is necessary to promote the protein interaction of NQO1 with p53, therefore, it increases the half-life of p53, and permits the cytotoxic effect of curcumin in cancer cells containing wild type p53. Our findings suggest that the use of curcumin may reactivate the p53 pathway in cancer cells with p53 wild-type.

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