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Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide-Gonearrestide
Li, Bin1; Lyu, Peng2; Xi, Xinping1,2; Ge, Lilin1,3; Mahadevappa, Ravikiran1; Shaw, Chris2; Kwok, Hang Fai1

In 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 invitro 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 invitro, invivo and exvivo 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-dependent kinases 4 (CDK4) and up-regulate the expression of cell cycle regulators/inhibitors-cyclin D3, p27, and p21. Furthermore, prediction of signalling pathways and potential binding sites used by Gonearrestide are also presented in this study.

KeywordAnticancer Mechanism Binding Sites Ms Ms Proteome Ngs Transcriptome Signalling Pathways Venom Library
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Indexed BySCI
WOS Research AreaCell Biology ; Research & Experimental Medicine
WOS SubjectCell Biology ; Medicine, Research & Experimental
WOS IDWOS:000442849700041
The Source to ArticleWOS
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Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorKwok, Hang Fai
Affiliation1.Faculty of Health Sciences, University ofMacau, Taipa, Macau, Macao
2.School of Pharmacy, Queen’s UniversityBelfast, Belfast, Northern Ireland, UK
3.School of Pharmacy, Jiangsu KeyLaboratory for Functional Substance ofChinese Medicine, Nanjing University ofChinese Medicine, Qixia District, Nanjing,China
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Li, Bin,Lyu, Peng,Xi, Xinping,et al. Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide-Gonearrestide[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2018,22(9):4460-4473.
APA Li, Bin.,Lyu, Peng.,Xi, Xinping.,Ge, Lilin.,Mahadevappa, Ravikiran.,...&Kwok, Hang Fai.(2018).Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide-Gonearrestide.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,22(9),4460-4473.
MLA Li, Bin,et al."Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide-Gonearrestide".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 22.9(2018):4460-4473.
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