期刊
MARINE DRUGS
卷 15, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/md15010020
关键词
tachyplesin I; glioblastoma multiforme; cancer stem cell; stable isotope dimethyl labeling; parallel reaction monitoring
资金
- Shenzhen Science and Technology Development Fund Project [JCYJ20130331151022276, GGJS20130331152344401]
- GDUHTP
- GDPRSFS
- Project of Guangdong Science and Technology Plan [2014A020217021]
- National Natural Science Foundation of China [31272474]
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.
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