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Review

Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review)

  • Authors:
    • Hua Luo
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Deyang Hospital of Sichuan Provincial People's Hospital, Deyang, Sichuan 618000, P.R. China
  • Article Number: 272
    |
    Published online on: July 28, 2025
       https://doi.org/10.3892/mmr.2025.13637
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Abstract

Tumor microenvironment (TME) dynamics and the critical dual role of hydrogen sulfide (H2S) in prostate cancer (PCa) biology are discussed in the present review. PCa remains one of the most prevalent malignancies in men, with advanced castration‑resistant PCa presenting substantial therapeutic challenges. H2S, an endogenous gaseous signaling molecule, is a key regulator of biological processes, including immune modulation, cell proliferation and apoptosis, during tumor progression. H2S exhibits paradoxical effects in PCa by promoting tumorigenesis and exerting context‑dependent antitumor activity. H2S mediates these outcomes through key signaling pathways, including the PI3K/AKT and MAPK/ERK pathways, which regulate tumor cell survival and metastasis. The present review emphasizes how H2S regulates tumor cell dynamics and immune interactions in a concentration‑dependent manner within the TME, making it a promising therapeutic target to overcome resistance to conventional treatments. Future research should prioritize translating these findings into clinical strategies, particularly through the development of H2S‑modulating therapies tailored to the TME, offering potential for overcoming resistance in advanced PCa.
View Figures

Figure 1

Dual roles of H2S in
prostate cancer and associated signaling pathways. Left (pro-tumor
effects; low H2S levels): PI3K/AKT/mTOR activation
promotes cell survival and proliferation (39,79);
VEGF-mediated angiogenesis supports nutrient supply (50). Right (antitumor effects; high
H2S levels): ROS accumulation induces oxidative damage
and apoptosis (68); caspase-3
activation induces programmed cell death (71); endoplasmic reticulum stress
triggers CHOP/GRP78-mediated apoptosis (105); and Treg suppression reverses
immune evasion (72,74). CHOP, C/EBP homologous protein;
GRP78, glucose-regulated protein 78; H2S, hydrogen
sulfide; ROS, reactive oxygen species; TME, tumor microenvironment;
Treg, regulatory T cell.
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Copy and paste a formatted citation
Spandidos Publications style
Luo H: Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review). Mol Med Rep 32: 272, 2025.
APA
Luo, H. (2025). Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review). Molecular Medicine Reports, 32, 272. https://doi.org/10.3892/mmr.2025.13637
MLA
Luo, H."Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review)". Molecular Medicine Reports 32.4 (2025): 272.
Chicago
Luo, H."Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review)". Molecular Medicine Reports 32, no. 4 (2025): 272. https://doi.org/10.3892/mmr.2025.13637
Copy and paste a formatted citation
x
Spandidos Publications style
Luo H: Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review). Mol Med Rep 32: 272, 2025.
APA
Luo, H. (2025). Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review). Molecular Medicine Reports, 32, 272. https://doi.org/10.3892/mmr.2025.13637
MLA
Luo, H."Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review)". Molecular Medicine Reports 32.4 (2025): 272.
Chicago
Luo, H."Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review)". Molecular Medicine Reports 32, no. 4 (2025): 272. https://doi.org/10.3892/mmr.2025.13637
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