Abstract
Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. It is the most invasive type of glioma developed from astrocytes. Until today, Temozolomide (TMZ) is the only standard chemotherapy for patients with GBM. Even though chemotherapy extends the survival of patients, there are many undesirable side effects, and most cases show resistance to TMZ. FL3 is a synthetic flavagline which displays potent anticancer activities, and is known to inhibit cell proliferation, by provoking cell cycle arrest, and leads to apoptosis in a lot of cancer cell lines. However, the effect of FL3 in glioblastoma cancer cells has not yet been examined. Hypoxia is a major problem for patients with GBM, resulting in tumor resistance and aggressiveness. In this study, we explore the effect of FL3 in glioblastoma cells under normoxia and hypoxia conditions. Our results clearly indicate that this synthetic flavagline inhibits cell proliferation and induced senescence in glioblastoma cells cultured under both conditions. In addition, FL3 treatment had no effect on human brain astrocytes. These findings support the notion that the FL3 molecule could be used in combination with other chemotherapeutic agents or other therapies in glioblastoma treatments.
Highlights
Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain
Flow cytometry using Annexin V and Propidium Iodide apoptosis assays revealed that FL3 treatment does not induce cell death in U87-MG cells (Fig. 2A)
Since it has been described that FL3 is not toxic in noncancer cells, we examined the effect of this molecule on normal human brain astrocytes in order to compare the results we obtained from treated U87-MG glioblastoma cells
Summary
Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. Cytotoxic effects of flavaglines has been reported in a lot of cancer cell lines, such as lung, breast, and colon c ancer[4], leading to the inhibition of proliferation and inducing cell cycle arrest or apoptosis in tumor cells. Glioblastoma (GBM) is the most common type of primary brain tumor[11,12], with a rapid growth and aggressive properties leading to an overall survival average of 14 to 18 m onths[13,14] This tumor can be found anywhere in the brain and is predominantly composed of abnormal astrocytes and a mix of different cell types. Afatinib is a well-known drug capable of crossing the blood brain barrier BBB21 and directly target the EGFR limiting the proliferation and invasion of glioblastoma cancer cells. All of the new targeted therapies (for example against EGFR) failed in clinical trials and GBM remain a challenge for oncologists
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