# Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway.
> 水素による子宮内膜癌増殖抑制：ROS/NLRP3/カスパーゼ-1/GSDMDを介したパイロトーシス経路の解析


## Abstract

This study examined whether hydrogen could induce pyroptosis in endometrial cancer cells via a ROS-dependent inflammasome pathway. Immunohistochemical and western blot analyses confirmed elevated expression of NLRP3, caspase-1, and GSDMD in human endometrial cancer specimens and derived cell lines. Hydrogen pretreatment elevated intracellular and mitochondrial ROS levels, upregulated pyroptosis-associated proteins, increased PI- and TUNEL-positive cell counts, and enhanced LDH and IL-1β release. Knockdown of GSDMD using shRNA lentivirus attenuated these effects, confirming GSDMD's functional role. In a xenograft mouse model, hydrogen-rich water administration significantly reduced tumor volume and weight, with tumor sections showing moderate-to-strong NLRP3, caspase-1, and GSDMD positivity. These findings indicate that hydrogen activates the NLRP3 inflammasome/GSDMD axis to drive pyroptotic cell death in endometrial cancer.

### Mechanism

Hydrogen elevates intracellular and mitochondrial ROS, activating the NLRP3 inflammasome. Subsequent caspase-1 cleavage of GSDMD triggers pyroptotic cell death in endometrial cancer cells, reducing tumor growth in vivo.

## Bibliographic

- **Authors**: Yang Y, Liu P, Bao W, Chen SL, Wu F, Zhu PY
- **Journal**: BMC Cancer
- **Year**: 2020 (2020-01-10)
- **PMID**: [31924176](https://pubmed.ncbi.nlm.nih.gov/31924176/)
- **DOI**: [10.1186/s12885-019-6491-6](https://doi.org/10.1186/s12885-019-6491-6)
- **PMC**: [PMC6954594](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954594/)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 31924176. https://h2-papers.org/en/papers/31924176
> **Source**: PubMed PMID [31924176](https://pubmed.ncbi.nlm.nih.gov/31924176/)
