Search

Background: Despite the development of various therapeutic approaches over the past decades, the treatment of glioblastoma multiforme (GBM) remains a major challenge. The extracellular adenosine-generating enzyme, CD73, is involved in the pathogenesis and progression of GBM, and targeting CD73 may represent a novel approach to treat this cancer. In this study, three-dimensional culture systems based on three hydrogel compositions were characterized and an optimal type was selected to simulate the GBM microenvironment. In addition, the effect of a CD73 inhibitor on GBM cell aggregates and spheroids was investigated as a potential therapeutic approach for this disease., Methods: Rheology measurements, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and cell proliferation assays were performed to analyze the synthesized hydrogel and select an optimal formulation. The viability of tumor cells in the optimal hydrogel was examined histologically and by confocal microscopy. In addition, the sensitivity of the tumor cells to the CD73 inhibitor was investigated using a cell proliferation assay and real-time PCR., Results: The data showed that the hydrogel containing 5 wt% gelatin and 5 wt% sodium alginate had better rheological properties and higher cell viability. Therefore, it could provide a more suitable environment for GBM cells and better mimic the natural microenvironment. GBM cells treated with CD73 inhibitors significantly decreased the proliferation rate and expression of VEGF and HIF1-α in the optimal hydrogel., Conclusion: Our current research demonstrates the great potential of CD73 inhibitor for clinical translation of cancer studies by analyzing the behavior and function of 3D tumor cells, and thus for more effective treatment protocols for GBM., Competing Interests: Declarations. Ethics approval and consent to participate: All protocols of this study were approved by Iran National Committee for Ethics in Biomedical Research (ID: IR.SEMUMS.REC.1400.032). Human and animal rights: No animals/humans were used for studies that are the basis of this research. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Recent studies suggest that Spirulina may have great therapeutic benefits due to its antioxidant and anti-inflammatory properties. The primary objective of this study was to evaluate the chemopreventive properties of the Spirulina microalgae (Spi) on the regression and survival of tumor, histopathological features of glioblastoma, and detection of the molecular mechanism of Spi. Tumor viability versus Spi was determined using the MTT assay. In vivo antitumor activity of Spi was studied using the glioblastoma model. After tumor induction, the animals were euthanized, and their brains were removed. Histological evaluation was performed for tumor size and manifestation. The mechanisms of the anticancer effects of Spi were investigated by evaluating the microRNAs and their targets. The results demonstrated that Spi inhibited C6 and U87 cell proliferation and induced cell death. Histopathologic results showed that the administration of Spi could delay the development of tumors and prolonged the survival of tumor-bearing animals. Furthermore, Spi significantly upregulated miR-34a and miR-125b that have a key role in the progression of PI3K/AKT/mTOR pathway. This is the first in vivo report on the chemo-preventive effect of Spi against glioblastoma, suggesting its potential use in the chemoprevention of this cancer and the antiglioma molecular mechanism of Spi., (© 2021 John Wiley & Sons, Ltd.)

Elaeagnus. angustifolia L. (EA) is a natural plant food with therapeutic and medicinal properties for treating various diseases such as rheumatoid arthritis and osteoporosis. Since herbal agents are origins of bioactive compounds, they can be applied in complementary treatment protocols. In this study, EA whole fruit extract's cytotoxic effects were investigated on both animal and human glioblastoma cancer cell lines. The extract of whole fruit of EA was obtained by maceration in ethanol. The phytochemical compounds were identified using high-performance liquid chromatography (HPLC). The MTT and LDH assays were performed to evaluate the cytotoxicity effect of the extract and the determination of cell death. Wound-healing assay and colony formation analysis were employed for migration and proliferation evaluation. Based on HPLC analysis, the main flavonoid components of the extract were included rutin and apigenin. The results demonstrated that EA extract at the dose of 125 to 2000 µg/ml and 61.5 to 2000 µg/ml inhibited C6 and U87 cells' viability and induced significant cell cytotoxicity at both 48 and 72 h incubation times. Besides, EA extract significantly inhibited cell migration and colony formation at 250 to 1000 µg/ml concentration. Overall, the results showed that EA extract could inhibit several stages in glioblastoma carcinogenesis in vitro. Therefore, it can be suggested as an anticancer in the clinical treatment approaches of glioblastoma cancer. [ABSTRACT FROM AUTHOR]