Abstract
Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, by using two complementary proteomic strategies (2D-DIGE and dimethyl isotope labeling-based shotgun proteomics), we explored the effect of tachyplesin I on the proteome of gliomaspheres, a three-dimensional growth model formed by a GBM cell line U251. In total, the expression levels of 192 proteins were found to be significantly altered by tachyplesin I treatment. Gene ontology (GO) analysis revealed that many of them were cytoskeleton proteins and lysosomal acid hydrolases, and the mostly altered biological process was related to cellular metabolism, especially glycolysis. Moreover, we built protein–protein interaction network of these proteins and suggested the important role of DNA topoisomerase 2-alpha (TOP2A) in the signal-transduction cascade of tachyplesin I. In conclusion, we propose that tachyplesin I might down-regulate cathepsins in lysosomes and up-regulate TOP2A to inhibit migration and promote apoptosis in glioma, thus contribute to its anti-tumor function. Our results suggest tachyplesin I is a potential candidate for treatment of glioma.
Highlights
Gliomas, the most common group of primary brain tumors, are subcategorized into astrocytomas, oligodendrogliomas and ependymomas
More and more studies have shown that certain cationic antimicrobial peptides (AMPs), which are toxic to bacteria but not to normal mammalian cells, exhibit a broad spectrum of cytotoxic activity against cancer cells [20]. tachyplesin I, which is isolated from hemocytes of the horseshoe crab, has been identified as a member of AMPs and exhibits cytotoxic activity against cancer cells
Our results showed that there was an increased topoisomerase 2-alpha (TOP2A) level in U251 gliomaspheres treated with tachyplesin I and it suggest the possible synergistic effect with TOP2A-targeting drugs, combination of which may be more effective on targeted goals and improve chemotherapy effect
Summary
The most common group of primary brain tumors, are subcategorized into astrocytomas, oligodendrogliomas and ependymomas. The short median survival of GBM is largely ascribed to the inevitable tumor recurrence. Recent research has paid more attention to the existence of glioma stem cells (GSCs), which are a subgroup of tumor cells with properties that resemble those of neural stem cells, and are able to drive tumorigenesis and likely contribute to rapid tumor recurrence [2]. These cells were first described more than ten years ago and have been demonstrated with the capability of multi-lineage differentiation, self-renewal and extensive proliferation [3]. GSCs can endure and even thrive in stressful
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