title: A novel spider peptide toxin suppresses tumor growth through dual signaling pathways.
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.
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Educational Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Deng
authors.forename: J
authors.initials: J
authors.lastname: Xiang
authors.forename: H
authors.initials: H
authors.lastname: Ma
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: D W-C
authors.initials: DW
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Liang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D013111:Spider Venoms / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D013111:Spider Venoms; C413374:p27 antigen; D045304:Cytochromes c; D053148:Caspase 3