Open Access

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

  • Published online on: April 5, 2024     https://doi.org/10.3892/or.2024.8730
  • Article Number: 71
  • Copyright: © Hsia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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May-2024
Volume 51 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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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