Abstract
Glioblastoma multiforme (GBM) is one of the most aggressive and common types of brain tumor. Due to its high proliferation ability, a high lethality rate has been observed with this malignant glial tumor. Terminalia catappa L. (T. catappa) is currently known to have anti-inflammatory and anti-carcinogenesis effects. However, few studies have examined the mechanisms of the leaf extracts of T. catappa (TCE) on GBM cells. In the current study, we demonstrated that TCE can significantly inhibit the migration and invasion capabilities of GBM cell lines without showing biotoxic effects. Matrix metalloproteinases-2 (MMP-2) activity and protein expression were attenuated by reducing the p38 phosphorylation involved in the mitogen-activated protein kinase (MAPK) pathway. By treating with TCE and/or p38 inhibitor (SB203580), we confirmed that p38 MAPK is involved in the inhibition of cell migration. In conclusion, our results demonstrated that TCE inhibits human GBM cell migration and MMP-2 expression by regulating the p38 pathway. These results reveal that TCE contains potent therapeutic compounds which could be applied for treating GBM brain tumors.
Highlights
Brain tumors are divided into two major types: cancerous and benign tumors
The results clearly showed that U251 and GBM8401 cell lines were not significantly affected at all treatment concentrations after 24 h and 48 h of treatment (Figure 1A,B)
Using a Boyden chamber-based assay, we found that the migration and invasion ability of both glioma cell lines were decreased significantly by treatment with T. catappa L. extract (TCE) (p < 0.05), except at the lowest concentration (5 μg/mL; Figure 2C–F)
Summary
The glioblastoma multiforme (GBM) is the most common type of brain tumor in humans [1]. Due to its high proliferation rate and invasiveness, GBM is recognized as a lethal brain tumor that shows a 2-year survival rate of less than 5% [2,3]. Multimodal treatment including feasible surgical resection, radiotherapy and adjuvant TMZ is still not sufficient, exhibiting survival rates of only around 14.6 months after diagnosis [6]. The chemotherapy drug TMZ can cause significant toxic side effects in nearly 20% of treated patients [7]. Due to this limitation of TMZ, the development of a new approach for GBM treatment is an important task today
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