Therapeutic potential of molecular hydrogen in ovarian cancer

Shang, L.; Xie, Fei; Li, Jiala; Zhang, Yating; Liu, Mengyu; Zhao, Pengxiang; Ma, Xuemei; LeBaron, Tyler W.

doi:10.21037/tcr.2018.07.09

Cited by 26 publications

(18 citation statements)

References 17 publications

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“…The results showed that hydrogen treatment suppressed migration, invasion, and the colony-forming ability in both C6 and U87 cells. We reported similar effects in a previous study on ovarian cancer cells [11]. A hallmark of GBM is the extensive invasion of tumor cells into the normal brain tissues and along the vascular tracks, which prevents complete resection of all malignant cells [3, 29].…”

Section: Discussionsupporting

confidence: 81%

“…The effects of molecular hydrogen on cancer have been reported in several types of tumors including skin squamous cell carcinomas [7], lung cancer [9, 10], ovarian cancer [11], thymic lymphoma [12], liver tumors [13, 17], renal cell carcinoma [14], and colon cancer [16, 18]. However, whether molecular hydrogen has an anti-tumor effect on GBM has remained unknown.…”

Section: Discussionmentioning

confidence: 99%

“…The hydrogen and oxygen concentration was much higher than that used in most of the previous studies (≈ 1–4% H 2 and 21% O 2 ). Although the effects of low concentration of molecular hydrogen have been extensively reported in many kinds of disease, some studies have used high concentration of molecular hydrogen, which also have anti-tumor effects [7, 9, 11]. Taken together, these studies may suggest that a high concentration of molecular hydrogen may be more effective on the treatment of cancer; however, the dose-response relationship of molecular hydrogen needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Several years later, Saitoh et al reported that neutral pH hydrogen-enriched electrolyzed water (NHE water) could achieve inhibition of tumor growth and of tumor invasion in an in vitro cell model [8]. Subsequent in vitro studies showed that molecular hydrogen could inhibit cancer cell proliferation [9–11], migration, invasion [9, 11], and colony formation [11] and induce cancer cell apoptosis [9, 10]. Several in vivo studies have demonstrated that molecular hydrogen could prevent carcinogenesis [12–14], inhibit cancer progression [9, 11], relieve the side effects of chemotherapy or radiotherapy [15–17], and enhance the anti-tumor effects of chemotherapeutic drugs [10, 18].…”

Section: Introductionmentioning

confidence: 99%

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Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation

et al. 2019

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Background Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Molecular hydrogen has been considered a preventive and therapeutic medical gas in many diseases including cancer. In our study, we sought to assess the potential role of molecular hydrogen on GBM. Methods The in vivo studies were performed using a rat orthotopic glioma model and a mouse subcutaneous xenograft model. Animals inhaled hydrogen gas (67%) 1 h two times per day. MR imaging studies were performed to determine the tumor volume. Immunohistochemistry (IHC), immunofluorescence staining, and flow cytometry analysis were conducted to determine the expression of surface markers. Sphere formation assay was performed to assess the cancer stem cell self-renewal capacity. Assays for cell migration, invasion, and colony formation were conducted. Results The in vivo study showed that hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM. IHC and immunofluorescence staining demonstrated that hydrogen treatment markedly downregulated the expression of markers involved in stemness (CD133, Nestin), proliferation (ki67), and angiogenesis (CD34) and also upregulated GFAP expression, a marker of differentiation. Similar results were obtained in the in vitro studies. The sphere-forming ability of glioma cells was also suppressed by hydrogen treatment. Moreover, hydrogen treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. Conclusions Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation

et al. 2019

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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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Micro/Nanomaterials‐Augmented Hydrogen Therapy

Zhou

Ekta

2019

Adv Healthcare Materials

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Hydrogen therapy is an emerging and promising therapy strategy of using molecular hydrogen as a new type of safe and effective therapeutic agent, exhibiting remarkable therapeutic effects on many oxidative stress‐/inflammation‐related diseases owing to its bio‐reductivity and homeostatic regulation ability. Different from other gaseous transmitters such as NO, CO, and H2S, hydrogen gas has no blood poisoning risk at high concentration because it does not affect the oxygen‐carrying behavior of blood red cells. Hydrogen molecules also have low aqueous solubility and high but aimless diffusibility, causing limited therapy efficacy in many diseases. To realize the site‐specific hydrogen delivery, controlled hydrogen release and combined therapy is significant but still challenging. Here, a concept of hydrogen nanomedicine to address the issues of hydrogen medicine by using functional micro/nanomaterials for augmented hydrogen therapy is proposed. In this review, various strategies of micro/nanomaterials‐augmented hydrogen therapy, including micro/nanomaterials‐mediated targeted hydrogen delivery, controlled hydrogen release, and nanocatalytic and multimodel enhancement of hydrogen therapy efficacy, are summarized, which can open a new window for treatment of inflammation‐related diseases.

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Therapeutic potential of molecular hydrogen in ovarian cancer

Cited by 26 publications

References 17 publications

Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation

Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation

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

Micro/Nanomaterials‐Augmented Hydrogen Therapy

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