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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\u00a0vitro 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, to dissect signalling pathway differences. Taken together the in\u00a0vitro, in\u00a0vivo and ex\u00a0vivo validation studies, it was proven that Gonearrestide could inhibit the growth of primary colon cancer cells and solid tumours by triggering cell cycle arrest in G1 phase through inhibition of cyclin\u2010dependent kinases 4 (CDK4) and up\u2010regulate the expression of cell cycle regulators\/inhibitors\u2014cyclin D3, p27, and p21. Furthermore, prediction of signalling pathways and potential binding sites used by Gonearrestide are also presented in this study.<\/jats:p>","DOI":"10.1111\/jcmm.13745","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T07:19:00Z","timestamp":1531293540000},"page":"4460-4473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Triggering of cancer cell cycle arrest by a novel scorpion venom\u2010derived peptide\u2014Gonearrestide"],"prefix":"10.1111","volume":"22","author":[{"given":"Bin","family":"Li","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences University of Macau Taipa, Macau Macao"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Lyu","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences University of Macau Taipa, Macau 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