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Article

NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study

  • Authors:
    • Alessia Garufi
    • Riccardo Pettinari
    • Laura Monteonofrio
    • Giulia Puliani
    • Ilaria Virdia
    • Marialuisa Appetecchia
    • Fabio Marchetti
    • Mara Cirone
    • Silvia Soddu
    • Gabriella D'Orazi
  • View Affiliations / Copyright

    Affiliations: Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS Regina Elena National Cancer Institute, I-00144 Rome, Italy, Chemistry Interdisciplinary Project (CHIP), School of Pharmacy, University of Camerino, I-62032 Camerino (MC), Italy, Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, I-00144 Rome, Italy, Chemistry Interdisciplinary Project (CHIP), School of Science and Technology, University of Camerino, I-62032 Camerino (MC), Italy, Department of Experimental Medicine, Sapienza University of Rome, Laboratory Affiliated to Pasteur Institute Italy Foundation Cenci Bolognetti, I-00161 Rome, Italy
  • Article Number: 36
    |
    Published online on: January 4, 2024
       https://doi.org/10.3892/or.2024.8695
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Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP‑NEN) are a group of rare tumors whose specific pathogenetic mechanisms of resistance to therapies have not been completely revealed yet. Chemotherapy is the main therapeutic approach in patients with GEP‑NEN, however, novel combination regimens and targeted therapy are continuously explored. In the present study, the anticancer effect of a novel Ruthenium (Ru)(II)‑Bisdemethoxycurcumin (Ru‑bdcurc) compound was evaluated in BON‑1 cell line, one of the few cell lines derived from GEP‑NEN, largely used in experimental research of this type of tumors. The experimental data revealed that the Ru‑bdcurc compound induced cell death in a dose‑dependent manner, in vitro. Biochemical studies demonstrated that, in response to the lower dose of treatment, BON‑1 cells activated the nuclear factor erythroid 2‑related factor 2 (NRF2) pathway with induction of some of its targets including catalase and p62 as well as of the antiapoptotic marker Bcl2, all acting as chemoresistance mechanisms. NRF2 induction associated also with increased expression of endogenous p53 which is reported to be dysfunctional in BON‑1 cells and to inhibit apoptosis. Genetic or pharmacologic targeting of NRF2 inhibited the activation of the NRF2 pathway, as well as of endogenous dysfunctional p53, in response to the lower dose of Ru‑bdcurc, increasing the cell death. To assess the interplay between NRF2 and dysfunctional p53, genetic targeting of p53 showed reduced activation of the NRF2 pathway in response to the lower dose of Ru‑bdcurc, increasing the cell death. These findings identified for the first time a possible dysfunctional p53/NRF2 interplay in BON‑1 cell line that can be a novel key determinant in cell resistance to cytotoxic agents to be evaluated also in GEP‑NEN.
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Copy and paste a formatted citation
Spandidos Publications style
Garufi A, Pettinari R, Monteonofrio L, Puliani G, Virdia I, Appetecchia M, Marchetti F, Cirone M, Soddu S, D'Orazi G, D'Orazi G, et al: NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study. Oncol Rep 51: 36, 2024.
APA
Garufi, A., Pettinari, R., Monteonofrio, L., Puliani, G., Virdia, I., Appetecchia, M. ... D'Orazi, G. (2024). NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study. Oncology Reports, 51, 36. https://doi.org/10.3892/or.2024.8695
MLA
Garufi, A., Pettinari, R., Monteonofrio, L., Puliani, G., Virdia, I., Appetecchia, M., Marchetti, F., Cirone, M., Soddu, S., D'Orazi, G."NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study". Oncology Reports 51.2 (2024): 36.
Chicago
Garufi, A., Pettinari, R., Monteonofrio, L., Puliani, G., Virdia, I., Appetecchia, M., Marchetti, F., Cirone, M., Soddu, S., D'Orazi, G."NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study". Oncology Reports 51, no. 2 (2024): 36. https://doi.org/10.3892/or.2024.8695
Copy and paste a formatted citation
x
Spandidos Publications style
Garufi A, Pettinari R, Monteonofrio L, Puliani G, Virdia I, Appetecchia M, Marchetti F, Cirone M, Soddu S, D'Orazi G, D'Orazi G, et al: NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study. Oncol Rep 51: 36, 2024.
APA
Garufi, A., Pettinari, R., Monteonofrio, L., Puliani, G., Virdia, I., Appetecchia, M. ... D'Orazi, G. (2024). NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study. Oncology Reports, 51, 36. https://doi.org/10.3892/or.2024.8695
MLA
Garufi, A., Pettinari, R., Monteonofrio, L., Puliani, G., Virdia, I., Appetecchia, M., Marchetti, F., Cirone, M., Soddu, S., D'Orazi, G."NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study". Oncology Reports 51.2 (2024): 36.
Chicago
Garufi, A., Pettinari, R., Monteonofrio, L., Puliani, G., Virdia, I., Appetecchia, M., Marchetti, F., Cirone, M., Soddu, S., D'Orazi, G."NRF2 activation in BON‑1 neuroendocrine cancer cells reduces the cytotoxic effects of a novel Ruthenium(II)‑curcumin compound: A pilot study". Oncology Reports 51, no. 2 (2024): 36. https://doi.org/10.3892/or.2024.8695
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