A Novel Spider Peptide Toxin Suppresses Tumor Growth Through Dual Signaling Pathways

作者：Liu, Z; Deng, M; Xiang, J; Ma, H; Hu, W; Zhao, Y; Li, D W C^*; Liang, S

来源：Current Molecular Medicine, 2012, 12(10): 1350-1360.

DOI：10.2174/156652412803833643

• Apoptosis
• cell proliferation
• gene expression
• mitochondria
• p27
• signal transduction
• spider peptide toxin
• tumor suppression

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 alpha-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.

• 出版日期2012-12
• 单位湖南师范大学