Hydrogen Therapy Shows Promise Against Endometrial Cancer in Lab Study
- Authors
- Ye Yang, Ping Yin Liu, Wei Bao, Song Jun Chen, Fang Su Wu, Ping Ya Zhu
- Journal
- BMC Cancer
- Year
- 2020
- DOI
- 10.1186/s12885-019-6491-6
- Study Type
- Cell Culture
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Endometrial Cancer
- Body System
- Reproductive System
TL;DR
Hydrogen treatment can promote a specific type of cell death in endometrial cancer, potentially offering a new approach to therapy.
Key Finding
Hydrogen treatment activated a cellular death pathway in endometrial cancer cells and reduced tumor growth in mice, suggesting a potential mechanism for how hydrogen might help fight this type of cancer.
Summary
Researchers investigated whether hydrogen could slow the growth of endometrial cancer (cancer of the uterine lining) by triggering a specific type of cell death called pyroptosis. Using cancer cells in dishes and tumors grown in mice, they found that hydrogen treatment increased reactive oxygen species (unstable molecules that damage cells) and activated a chain of proteins that led cancer cells to die through pyroptosis, while the treatment reduced tumor size in mice.
Practical Takeaway
This early-stage research in cells and mice suggests hydrogen may have anti-cancer properties through a specific biological mechanism, but these findings have not been tested in humans. Much more research, including human clinical trials, would be needed before hydrogen could be considered a treatment for endometrial cancer.
Abstract
Background: Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis. Methods: We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation. Results: We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway. Conclusions: This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.