The effect of Azo-dyes on glioblastoma cells in vitro.

Despite the multidisciplinary standard treatment of glioblastoma (GB) consisting of maximal surgical resection, followed by radiotherapy (RT) plus concomitant chemotherapy with temozolomide (TMZ), the majority of patients experience tumor progression and almost universal mortality. In recent years, efforts have been made to create new agents for GB treatment, of which azo-dyes proved to be potential candidates, showing antiproliferative effects by inducing apoptosis and by inhibiting different signaling pathways. In this study we evaluated the antiproliferative the effect of six azo-dyes and TMZ on a low passage human GB cell line using MTT assay. We found that all compounds proved antiproliferative properties on GB cells. At equimolar concentrations azo-dyes induced more cytotoxic effect than TMZ. We found that Methyl Orange required the lowest IC50 for 3 days of treatment (26.4684 µM), whilst for 7 days of treatment, two azo dyes proved to have the highest potency: Methyl Orange IC50 = 13.8808 µM and Sudan I IC50 = 12.4829 µM. The highest IC50 was determined for TMZ under both experimental situations. Conclusions: Our research represents a novelty, by offering unique valuable data regarding the azo-dye cyototoxic effects in high grade brain tumors. This study may focus the attention on azo-dye agents that may represent an insufficient exploited source of agents for cancer treatment.

Glioblastoma Stem Cells-Useful Tools in the Battle against Cancer.

Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy-resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. This review provides an overview of the molecular features, microenvironment, detection, and targeting strategies of GSCs, an essential information required for an efficient therapy. Despite the outstanding results in oncology, researchers are still developing novel strategies, of which one could be targeting the GSCs present in the hypoxic regions and invasive edge of the glioblastoma.

Combined Effects of Doxorubicin and Temozolomide in Cultured Glioblastoma Cells.

The oncological field benefits of extensive medical research and various types of cancer notice improvements, however glioblastoma multiforme remains one of the deadliest cancers in humans with virtually no advance in survival and clinical outcome. Temozolomide, the FDA approved drug for glioblastoma, faces numerous challenges such as resistance and side effects. To overcome these challenges, many combination therapies are currently studied. The present study analyses the effects of temozolomide in combination with doxorubicin on a glioblastoma cell line. Our results showed that both drugs displayed a cytotoxic effect on the studied cells in single administration (55% for 100µM temozolomide at 14 days, 53% for 100µM doxorubicin at 14 days), but without a synergistic effect in dual therapy. Although the results failed to produce the expected effect, they propose new research perspectives in the future.

The Effect of Β-Arrestin2 Overexpression Regarding Viability and Temozolomide Treatment in High-Grade Glioma Cells.

The ß-arrestins (ß-arr) family are proteins that regulate the signaling and trafficking of various G protein-coupled receptors. Out of the four members, ß-arr 1 and 2 have been proven as essential actors behind different processes that lead to the progression of cancer as cell proliferation, migration, invasion and metastasis. In addition to this, these proteins are also capable of transmitting anti-apoptotic signals, influence tumor growth rate and drug resistance. Several studies have demonstrated that ß-arr 2 overexpression corelates with an impaired overall survival and also showed that it may mediate multidrug resistance in certain types of cancer. In the current study we analyzed the effect of ß-arr 2 overexpression on proliferation and how it affects Temozolomide (TMZ) response on the CL2:6 High Grade Glioma (HGG) cell line. We observed contradictory results after transfection, with ß-arr 2 overexpressing cells having a superior proliferation rate after 24 and 48h, when compared to untransfected cells, while the opposite was noted after 72h. In terms of response to TMZ, we observed a similar contradictory pattern with modest differences between doses being observed at 24h, while the smallest and largest doses in our experiment produced opposite effects after 48h and 72h. This further underscores the scarcity of information regarding the exact roles and the importance of ß-arrs in the intrinsic mechanisms which govern cancer cells.

ELTD1-An Emerging Silent Actor in Cancer Drama Play.

The epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 (ELTD1), is a member of the G-protein coupled receptors (GPCRs) superfamily. Although discovered in 2001, ELTD1 has been investigated only by a few research groups, and important data about its role in normal and tumor cells is still missing. Even though its functions and structure are not yet fully understood, recent studies show that ELTD1 has a role in both physiological and pathological angiogenesis, and it appears to be a very important biomarker and a molecular target in cancer diseases. Upregulation of ELTD1 in malignant cells has been reported, and correlated with poor cancer prognosis. This review article aims to compile the existing data and to discuss the current knowledge on ELTD1 structure and signaling, and its role in physiological and neoplastic conditions.

Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches.

From all central nervous system tumors, gliomas are the most common. Nowadays, researchers are looking for more efficient treatments for these tumors, as well as ways for early diagnosis. Receptor tyrosine kinases (RTKs) are major targets for oncology and the development of small-molecule RTK inhibitors has been proven successful in cancer treatment. Mutations or aberrant activation of the RTKs and their intracellular signaling pathways are linked to several malignant diseases, including glioblastoma. The progress in the understanding of malignant glioma evolution has led to RTK targeted therapies with high capacity to improve the therapeutic response while reducing toxicity. In this review, we present the most important RTKs (i.e. EGFR, IGFR, PDGFR and VEGFR) currently used for developing cancer therapeutics together with the potential of RTK-related drugs in glioblastoma treatment. Also, we focus on some therapeutic agents that are currently at different stages of research or even in clinical phases and proved to be suitable as re-purposing candidates for glioblastoma treatment.