RESUMEN

BACKGROUND: Plant extract therapy has been the cornerstone of cancer treatment for many years. The natural component curcumin demonstrated antineoplastic effects on different type of tumor cells. In this study, we explored the effectiveness of curcumin against low-passage human primary glioblastoma (GB) cell cultures. MATERIALS AND METHODS: Early passage GB cell cultures (GB3B, GB4B, and GB5B) were established from fresh samples tissue obtained from GB patients. Growth rate (GR) and doubling time (DT) was determined for each cell line. The cytotoxic effect of curcumin was quantified by hemocytometer cell counting, using trypan blue. To study the changes in cell shape, GB cells exposed to a concentration corresponding to inhibitory concentration 50 (IC50) of curcumin were studied by phase-contrast microscopy by capturing images during the treatment. RESULTS: Our results showed that GB cells proliferate with a GR of 0.2872 and a DT of 2.41 days for GB3B, a GR of 0.2787 and a DT of 2.49 days for GB4B, and a GR of 0.2787 and a DT of 2.49 days for GB5B. Curcumin induced cell death in GB cells in a time- and dose-dependent manner. The IC50 for GB3B was 46.4 µM, for GB4B was 78,3 µM, and for GB5B was 47.7 µM. Phase contrast microscopy showed that cultures treated with curcumin in a concentration corresponding to IC50 contained rounded cells and cell fragments, 72 h after the treatment. CONCLUSIONS: The results of the present investigation proved that curcumin is a natural compound potentially useful in the fight against GB.

Asunto(s)

Antineoplásicos/farmacología , Curcumina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glioblastoma , Humanos , Células Tumorales Cultivadas

RESUMEN

Glioblastoma (GB) is highly vascularised tumour, known to exhibit enhanced infiltrative potential. One of the characteristics of glioblastoma is microvascular proliferation surrounding necrotic areas, as a response to a hypoxic environment, which in turn increases the expression of angiogenic factors and their signalling pathways (RAS/RAF/ERK/MAPK pathway, PI3K/Akt signalling pathway and WTN signalling cascade). Currently, a small number of anti-angiogenic drugs, extending glioblastoma patients survival, are available for clinical use. Most medications are ineffective in clinical therapy of glioblastoma due to acquired malignant cells or intrinsic resistance, angiogenic receptors cross-activation and redundant intracellular signalling, or the inability of the drug to cross the blood-brain barrier and to reach its target in vivo. Researchers have also observed that GB tumours are different in many aspects, even when they derive from the same tissue, which is the reason for personalised therapy. An understanding of the molecular mechanisms regulating glioblastoma angiogenesis and invasion may be important in the future development of curative therapeutic approaches for the treatment of this devastating disease.

RESUMEN

Growth factor receptors dysfunction has previously been correlated with glioma cell proliferation, ability to evade apoptosis, neo-angiogenesis and resistance to therapy. Antineoplastic molecules targeting growth factor receptors are in clinical handling, however the efficacy of these compounds has often been limited by the signaling redundancy. Here, we analyzed the effect of AG1433 (a PDGFR inhibitor), SU1498 (a VEGFR inhibitor) and BEZ235 (a PI3K/Akt/mTOR signaling pathways inhibitor) on glioblastoma cells in vitro. For this study, we used a low passage glioblastoma cell line (GB9B). Assessment of cell number over 72 h showed that the growth rate was 0.3024 and the doubling time of GB9B was 2.29 days. Similar cytotoxic effects were observed by using AG1433 and SU1498 treatment, while dual PI3K/Akt/mTOR inhibition by BEZ235 was more efficient in killing glioblastoma cells than individual PDGFR or VEGFR targeting. In SU1498 treated cells, caspase 3 activity was detected 3 hours after the treatment, while activation of caspase 8 and 9 was detected 48 hours later. AG1433 treatment induced caspase 3, 8 and 9, 3 hours after the treatment. BEZ235 treatment resulted in early caspase 3 and 8 activation, 3 hours after the treatment and an activation of caspase 9, 8 hours later.

Asunto(s)

Glioblastoma/tratamiento farmacológico , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proliferación Celular/efectos de los fármacos , Glioblastoma/patología , Humanos , Imidazoles , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Quinolinas , Serina-Treonina Quinasas TOR , Factor A de Crecimiento Endotelial Vascular/genética

RESUMEN

In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors.

RESUMEN

ABSTRACT: The development and function of the nervous system is dependent on many growth factors and their signaling. Tropomyosin-receptor-kinase receptor family controls synaptic strength and plasticity in the mammalian nervous system. Dysregulation of Tropomyosin-receptor-kinase receptors signaling can lead to neural developmental disorders and has been reported in certain diseases of the nervous system. Apart from their role in the nervous system, these tyrosine kinase receptors are also involved in cancer biology. Tropomyosin-receptor-kinases and their ligands, neurotrophins, are also involved in neural precursor stem cells differentiation. This review focuses on Tropomyosin-receptor-kinases, the most abundant receptors in mammalian nervous system.