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Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide -- Gonearrestide
Li, B.; Lyu, P.; Xi, X.; Mahadevappa, R.; Ge, L.; Shaw, C.; Kwok, H. F.
2018-06-01
Source PublicationJournal of Cellular and Molecular Medicine
ISSN1582-4934
PagesDOI:10.1111/jcmm.13745---
AbstractIn this study, a novel scorpion venom-derived peptide named Gonearrestide was identified in an in-house constructed scorpion venom library through a combination of high throughput NGS transcriptome and MS/MS proteome platform. In total, 238 novel peptides were discovered from two scorpion species; and 22 peptides were selected for further study after a battery of functional prediction analysis. Following a series of bioinformatics analysis alongside with in vitro biological functional screenings, Gonearrestide was found to be a highly potent anticancer peptide which acts on a broad spectrum of human cancer cells while causing few if any observed cytotoxic effects on epithelial cells and erythrocytes. We further investigated the precise anticancer mechanism of Gonearrestide by focusing on its effects on the colorectal cancer cell line, HCT116. NGS RNA-sequencing was employed to obtain full gene expression profiles in HCT116 cells, cultured in the presence and absence of Gonearrestide, in order to dissect signaling pathway differences. Taken together the in vitro, in vivo and ex vivo validation studies, it was proven that Gonearrestide could inhibit the growth of primary colon cancer cells and solid tumors by triggering cell cycle arrest in G1 phase through inhibition of cyclin-dependent kinases 4 (CDK4) and up-regulate the expression of cell cycle regulators/inhibitors - cyclin D3, p27 and p21. Furthermore, prediction of signaling pathways and potential binding sites used by Gonearrestide are also presented in this study.
KeywordVenom library NGS transcriptome MS/MS proteome Anticancer mechanism Signaling pathways Binding sites
Language英語English
The Source to ArticlePB_Publication
PUB ID36317
Document TypeJournal article
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorKwok, H. F.
Recommended Citation
GB/T 7714
Li, B.,Lyu, P.,Xi, X.,et al. Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide -- Gonearrestide[J]. Journal of Cellular and Molecular Medicine, 2018, DOI:10.1111/jcmm.13745---.
APA Li, B.., Lyu, P.., Xi, X.., Mahadevappa, R.., Ge, L.., Shaw, C.., & Kwok, H. F. (2018). Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide -- Gonearrestide. Journal of Cellular and Molecular Medicine, DOI:10.1111/jcmm.13745---.
MLA Li, B.,et al."Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide -- Gonearrestide".Journal of Cellular and Molecular Medicine (2018):DOI:10.1111/jcmm.13745---.
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