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

Abstract

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.

Biological effects of selective COX-2 inhibitor NS398 on human glioblastoma cell lines

“…These markers were also analyzed in relative adherent cells to highlight the differences with respect to neurosphere-forming cells (Table 1). In accordance with previous reports [8,63,64], the percentages…”

Hydrogen Gas in Cancer Treatment

“…In vitro study indicated that hydrogen gas inhibited several markers involved in stemness, resulting in the suppression of sphere formation, cell migration, invasion, and colony formation of glioma cells. By inhaling hydrogen gas (67%) 1 h, 2 times per day, the GBM growth was significantly inhibited, and the survival rate was improved in a rat orthotopic glioma model, suggesting that hydrogen might be a promising agent in the treatment of GBM (100).…”

Antitumor Activity of Protons and Molecular Hydrogen: Underlying Mechanisms

“…The invasive properties of glioblastoma are a key problem for curative treatment if a surgical resection is impracticable. The experimental in vivo studies showed that H 2 inhalation could suppress glioblastoma tumor growth, prolonging the survival of mice with glioblastoma [ 56 ]. In a recent study, data show that, in a patient diagnosed with lung cancer with metastases, H 2 gas monotherapy was associated with a significant effective control of tumors [ 57 ].…”