Abstract
Spider venom is a large pharmacological repertoire containing many biologically active peptides, which may have a potent therapeutic implication. Here we investigated a peptide toxin, named lycosin-I, isolated from the venom of the spider Lycosa singoriensis. In contrast to most spider peptide toxins adopting inhibitor cystine knot (ICK) motif, lycosin-I shows a linear amphipathic alpha-helical conformation, common to α-helical host defense peptides. Lycosin-I displays strong ability to inhibit cancer cell growth in vitro and can effectively suppresses tumor growth in vivo. Mechanistically, it activates the mitochondrial death pathway to sensitize cancer cells for apoptosis, as well as up-regulates p27 to inhibit cell proliferation. Taken together, our results provide the first evidence that a spider toxin can effectively suppress tumorigenesis through activation of dual signaling pathways. In addition, lycosin-I may be a useful structural lead for the development of novel anticancer drugs.
Keywords: Apoptosis, cell proliferation, gene expression, mitochondria, p27, signal transduction, spider peptide toxin, tumor suppression, therapeutic agents, neurotoxins, lycosin-I, anticancer peptides, cancer, anticancer drugs, carcinoma
Current Molecular Medicine
Title:A Novel Spider Peptide Toxin Suppresses Tumor Growth Through Dual Signaling Pathways
Volume: 12 Issue: 10
Author(s): Z. Liu, M. Deng, J. Xiang, H. Ma, W. Hu, Y. Zhao, D.W.-C. Li and S. Liang
Affiliation:
Keywords: Apoptosis, cell proliferation, gene expression, mitochondria, p27, signal transduction, spider peptide toxin, tumor suppression, therapeutic agents, neurotoxins, lycosin-I, anticancer peptides, cancer, anticancer drugs, carcinoma
Abstract: Spider venom is a large pharmacological repertoire containing many biologically active peptides, which may have a potent therapeutic implication. Here we investigated a peptide toxin, named lycosin-I, isolated from the venom of the spider Lycosa singoriensis. In contrast to most spider peptide toxins adopting inhibitor cystine knot (ICK) motif, lycosin-I shows a linear amphipathic alpha-helical conformation, common to α-helical host defense peptides. Lycosin-I displays strong ability to inhibit cancer cell growth in vitro and can effectively suppresses tumor growth in vivo. Mechanistically, it activates the mitochondrial death pathway to sensitize cancer cells for apoptosis, as well as up-regulates p27 to inhibit cell proliferation. Taken together, our results provide the first evidence that a spider toxin can effectively suppress tumorigenesis through activation of dual signaling pathways. In addition, lycosin-I may be a useful structural lead for the development of novel anticancer drugs.
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Liu Z., Deng M., Xiang J., Ma H., Hu W., Zhao Y., Li D.W.-C. and Liang S., A Novel Spider Peptide Toxin Suppresses Tumor Growth Through Dual Signaling Pathways, Current Molecular Medicine 2012; 12 (10) . https://dx.doi.org/10.2174/156652412803833643
DOI https://dx.doi.org/10.2174/156652412803833643 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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