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Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells

  • Authors:
    • Yi-Jan Hsia
    • Zhang-Min Lin
    • Taolan Zhang
    • Tz-Chong Chou
  • View Affiliations / Copyright

    Affiliations: Dental Department and Division of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan, R.O.C., Cathay Medical Research Institute, Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C., The First Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, P.R. China
    Copyright: © Hsia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 71
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    Published online on: April 5, 2024
       https://doi.org/10.3892/or.2024.8730
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Abstract

Cancer cells are characterized by increased glycolysis, known as the Warburg effect, which leads to increased production of cytotoxic methylglyoxal (MGO) and apoptotic cell death. Cancer cells often activate the protective nuclear factor erythroid 2‑related factor2 (Nrf2)/glyoxalase1 (Glo1) system to detoxify MGO. The effects of sodium butyrate (NaB), a product of gut microbiota, on Nrf2/Glos/MGO pathway and the underlying mechanisms in prostate cancer (PCa) cells were investigated in the present study. Treatment with NaB induced the cell death and reduced the proliferation of PCa cells (DU145 and LNCap). Moreover, the protein kinase RNA-like endoplasmic reticulum kinase/Nrf2/Glo1 pathway was greatly inhibited by NaB, thereby accumulating MGO-derived adduct hydroimidazolone (MG-H1). In response to a high amount of MGO, the expression of Nrf2 and Glo1 was attenuated, coinciding with an increased cellular death. NaB also markedly inhibited the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (Stat3) pathway. Conversely, co‑treatment with Colivelin, a Stat3 activator, significantly reversed the effects of NaB on Glo1 expression, MG-H1 production, and the cell migration and viability. As expected, overexpression of Stat3 or Glo1 reduced NaB‑induced cell death. The activation of calcium/calmodulin dependent protein kinase II gamma and reactive oxygen species production also contributed to the anticancer effect of NaB. The present study, for the first time, demonstrated that NaB greatly increases MGO production through suppression of the JAK2/Stat3/Nrf2/Glo1 pathway in DU145 cells, a cell line mimicking castration‑resistant PCa (CRPC), suggesting that NaB may be a potential agent for PCa therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Hsia Y, Lin Z, Zhang T and Chou T: Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells. Oncol Rep 51: 71, 2024.
APA
Hsia, Y., Lin, Z., Zhang, T., & Chou, T. (2024). Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells. Oncology Reports, 51, 71. https://doi.org/10.3892/or.2024.8730
MLA
Hsia, Y., Lin, Z., Zhang, T., Chou, T."Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells". Oncology Reports 51.5 (2024): 71.
Chicago
Hsia, Y., Lin, Z., Zhang, T., Chou, T."Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells". Oncology Reports 51, no. 5 (2024): 71. https://doi.org/10.3892/or.2024.8730
Copy and paste a formatted citation
x
Spandidos Publications style
Hsia Y, Lin Z, Zhang T and Chou T: Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells. Oncol Rep 51: 71, 2024.
APA
Hsia, Y., Lin, Z., Zhang, T., & Chou, T. (2024). Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells. Oncology Reports, 51, 71. https://doi.org/10.3892/or.2024.8730
MLA
Hsia, Y., Lin, Z., Zhang, T., Chou, T."Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells". Oncology Reports 51.5 (2024): 71.
Chicago
Hsia, Y., Lin, Z., Zhang, T., Chou, T."Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells". Oncology Reports 51, no. 5 (2024): 71. https://doi.org/10.3892/or.2024.8730
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