Hydrogen gas inhibits lung cancer progression through targeting SMC3

Wang, Dongchang; Wang, Lifei; Zhang, Yu; Zhao, Yi‐Fang; Chen, Gang

doi:10.1016/j.biopha.2018.05.055

Cited by 78 publications

(79 citation statements)

References 40 publications

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“…In the past 10 years, H 2 has been used to treat cancer and metabolic disease or to correct ischemia and reperfusion injury of various organs, taking advantage of its high bio-safety [20][21][22]. With respect to cancer, hydrogen can inhibit cellular activity, proliferation, invasion, and migration in a dose-and time-dependent manner; promote apoptosis in cervical cancer, breast cancer, cutaneous melanoma [23], ovarian cancer [24], lung cancer [25], colon cancer [26], thymic lymphoma [27], Ehrlich ascites tumor cells [28], oral squamous cell carcinoma, and fibrosarcoma cells [29]; reduce tumor volume and weight; and inhibit tumor growth in xenografted mice, thus prolonging the survival of tumor-bearing mice [23]. H 2 also reduces renal toxicity in patients undergoing radiotherapy and chemotherapy [30].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

et al. 2020

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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 hydrogensupplemented 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 pyroptosisrelated 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 antitumor effects in the clinical management of endometrial cancer.

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Section: Introductionmentioning

confidence: 99%

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

et al. 2020

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“…Hydrogen has been used to treat various states associated with oxidative stress, including trauma (15), neurodegenerative disease (16), inflammatory disease (17), organ transplantation, metabolic syndrome (18), diabetes mellitus (19), sepsis (20), burns (21), adverse reactions to chemotherapy (22), radiation injury (23), hearing disorders and preeclampsia (24). There are several studies on the preventive and therapeutic effects of hydrogen on various diseases, including cancer (25)(26)(27). Notably, it was reported that molecular hydrogen activates PGC-1α (28), which is a positive regulator of mitochondrial biogenesis and respiration, adaptive thermogenesis, gluconeogenesis and a number of…”

Section: Introductionmentioning

confidence: 99%

Hydrogen gas restores exhausted CD8+ T�cells in patients with advanced colorectal cancer to improve prognosis

Akagi

Baba

2018

Oncol Rep

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Exhausted cluster of differentiation (CD)8 + T cells lose immunological activity due to mitochondrial dysfunction caused by peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) inactivation, resulting in a poor prognosis in patients with cancer. As hydrogen gas was recently reported to activate PGC-1α, the present study investigated whether it restores exhausted CD8 + T cells to improve prognosis in patients with stage IV colorectal cancer. A total of 55 patients with histologically and clinically diagnosed stage IV colorectal carcinoma were enrolled between July 2014 and July 2017. The patients inhaled hydrogen gas for 3 h/day at their own homes and received chemotherapy at the Tamana Regional Health Medical Center (Tamana, Kumamoto, Japan). The CD8 + T cells were isolated from the peripheral blood and their phenotype was analyzed by flow cytometry. It was found that exhausted terminal programmed cell death 1 (PD-1) + CD8 + T cells in the peripheral blood are independently associated with worse progression-free survival (PFS) and overall survival (OS). Notably, hydrogen gas decreased the abundance of exhausted terminal PD-1 + CD8 + T cells, increased that of active terminal PD-1 -CD8 + T cells, and improved PFS and OS times, suggesting that the balance between terminal PD1 + and PD1 -CD8 + T cells is critical for cancer prognosis. Therefore, a novel system for patient classification (category 1-4) was developed in the present study based on these two indices to assist in predicting the prognosis and therapeutic response.Collectively, the present results suggested that hydrogen gas reverses imbalances toward PD-1 + CD8 + T cells to provide an improved prognosis.

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“…Their study showed that hydrogen could down-regulate the expression of SMC3, structural maintenance of chromosomes 5 (SMC5), structural maintenance of chromosomes 6 (SMC6) and Nipped-B homolog (Drosophila) (NIBPL). They found that hydrogen translocated SMC3 during cell division, resulting in decreased cell stability and enhanced SMC3 ubiquitination in A549 and H1975 lung cancer cell lines [23]. This study suggested that hydrogen gas may inhibit the progression of lung cancer by down-regulating SMC3.…”

Section: Hydrogen Delays the Progression Of Cancermentioning

confidence: 84%

“…Recently, Wang D et al found that hydrogen gas inhibited the viability, migration and invasion of lung cancer cells in vitro; and inhibited tumor growth in vivo [23]. They also discovered that hydrogen inhibits lung cancer progression by down-regulating the expression and structural stability of structural maintenance of chromosomes 3 (SMC3).…”

Section: Hydrogen Delays the Progression Of Cancermentioning

confidence: 99%

Progress in the Use of Molecular Hydrogen for Cancer Treatment

Du¹,

Peng²,

Liu³

et al. 2019

Journal of Nutritional Oncology

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Molecular hydrogen is an effective antioxidant. Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases. The possibility of using hydrogen in the treatment of cancer was first discovered in 1975, and in recent studies, researchers have reported numerous positive effects of hydrogen in cancer therapy, including: 1) the alleviation of complications caused by chemotherapy; 2) a reduction of complications caused by radiotherapy; 3) delays in the progression of cancer; and 4) enhanced efficacy of conventional therapy when used in combination with hydrogen. This article reviews the research progress in the use of hydrogen in the treatment of cancer, and proposes future directions for research in this field.

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Hydrogen gas inhibits lung cancer progression through targeting SMC3

Cited by 78 publications

References 40 publications

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

Hydrogen gas restores exhausted CD8+ T�cells in patients with advanced colorectal cancer to improve prognosis

Progress in the Use of Molecular Hydrogen for Cancer Treatment

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