Selenium nanoparticles reduce glucose metabolism and promote apoptosis of glioma cells through reactive oxygen species-dependent manner

Abstract

Gliomas are the most common, malignant, and lethal tumors in adults. Furthermore, gliomas are highly resistant to current chemotherapeutic drugs. Thus, new effective anticancer drugs for glioma are urgently needed. Selenium nanoparticles have been reported to have potent anti-tumor activity, although the specific mechanism is not fully understood. This study aimed to test the anti-tumor effect of selenium nanoparticles and its mechanism. We used selenium nanoparticles to treat commercial glioma cell lines, and patient-derived glioma cells, and then used the MTT assay to determine selenium nanoparticles effect against these. Apoptotic cell death was determined by annexin V-Fluos staining kit. Glucose uptake, lactate, and adenosine triphosphate production, together with hexokinase 2 and pyruvate kinase activities were measured to determine the glucose metabolism level. Reactive oxygen species production was tested using 2′,7′-dichlorodihydrofluorescein diacetate. Our results showed that selenium nanoparticles had a potent cytotoxic effect in glioma cells, regardless of whether they were drug-resistant or not, whereas it showed less toxic effect in normal healthy cells. Further tests showed that selenium nanoparticles treatment leads to apoptotic cell death enhancement and glucose metabolism reduction, and this process was in a reactive oxygen species pathway-dependent manner. These results may provide a novel direction for glioma therapy in the future.

Therapeutic Potential of Selenium in Glioblastoma

“…Other laboratory studies confirmed similar results in glioblastoma treatment with some modifications in surface decorating ligands for Se nanoparticles like HER2 and arginylglycylaspartic acid (You et al, 2016;Jardim et al, 2017;Song et al, 2018). Also, it has been demonstrated that Se-containing nanoparticles treatment significantly reduced both the bioenergy metabolism and the invasion of drug-resistant glioma cells (Xu B. et al, 2020), while benign cells remained viable indicating that Se toxicity is selective for glioma cells.…”

Sialic Acid—Modified Nanoparticles—New Approaches in the Glioma Management—Perspective Review

“…First, the decoration of nanoparticles by sialic acids can enhance their delivery to tumor cells and therapeutic efficacy. The recent study by Xu et al confirmed the strong apoptotic action of selenium nanocarriers against glioma cells [ 75 ]. However, their modification by sialic acid significantly increases the uptake by malignant cells and potentiates the apoptotic effect.…”

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

“…• In vitro: Selenium NP (Xu et al, 2020), MNP (Shen et al, 2017) • In vivo: MP (Cheng Y. et al, 2016;Kim et al, 2010)…”

“…2019; Shi et al, 2019;Sousa et al, 2019;Ye et al, 2019;Zhang et al, 2019;Zhao et al, 2019;ZhuGe et al, 2019;Alves et al, 2020;Caban-Toktas et al, 2020;Chung et al, 2020;Ferreira et al, 2020;Kazmi et al, 2020;Liang et al, 2020;Martinez-Rovira et al, 2020;Meng et al, 2020;Roberts et al, 2020;Ullah et al, 2020;Wang H. et al, 2020;Wang X. et al, 2020;Xu et al, 2020;Zhu et al, 2020; see Table 3 for examples of ligand targeting in glioma research). Another active targeting method to increase functional specificity of NPs that are used as gene delivery systems is the transcriptional targeting, which can occur at a transcriptional or posttranscriptional level (Golombek et al, 2018).…”

“…Here, the delivered gene includes a tumor-specific promoter (highly functional only in cancer cells), which will secure a well-localized expression of the transgene, limited to occur only inside the cancer cells of interest. Posttranscriptional regulations of the product encoded by the exogenously delivered gene are achieved by controlling RNA splicing, RNA stability, and initiation of the RNA translation once it is present in the cancer cell (Maier-Hauff et al, 2007;Kim et al, 2010;Wegscheid et al, 2014;Cheng Y. et al, 2016;Shen et al, 2017;Yu et al, 2017;Hua et al, 2018;Daniel et al, 2019;Denora et al, 2019;Dufort et al, 2019;Kunoh et al, 2019;Luque-Michel et al, 2019;Ruan et al, 2019;Rego et al, 2019Rego et al, , 2020Shi et al, 2019;Sousa et al, 2019;Ye et al, 2019;Zhang et al, 2019;Zhao et al, 2019;ZhuGe et al, 2019;Alves et al, 2020;Caban-Toktas et al, 2020;Chung et al, 2020;Ferreira et al, 2020;Kazmi et al, 2020;Liang et al, 2020;Martinez-Rovira et al, 2020;Meng et al, 2020;Roberts et al, 2020;Ullah et al, 2020;Wang H. et al, 2020;Wang X. et al, 2020;Xu et al, 2020;Zhu et al, 2020).…”