title: Cytocidal actions of parasporin-2, an anti-tumor crystal toxin from Bacillus thuringiensis.
abstract: Parasporin-2, a new crystal protein derived from noninsecticidal and nonhemolytic Bacillus thuringiensis, recognizes and kills human liver and colon cancer cells as well as some classes of human cultured cells. Here we report that a potent proteinase K-resistant parasporin-2 toxin shows specific binding to and a variety of cytocidal effects against human hepatocyte cancer cells. Cleavage of the N-terminal region of parasporin-2 was essential for the toxin activity, whereas C-terminal digestion was required for rapid cell injury. Protease-activated parasporin-2 induced remarkable morphological alterations, cell blebbing, cytoskeletal alterations, and mitochondrial and endoplasmic reticulum fragmentation. The plasma membrane permeability was increased immediately after the toxin treatment and most of the cytoplasmic proteins leaked from the cells, whereas mitochondrial and endoplasmic reticulum proteins remained in the intoxicated cells. Parasporin-2 selectively bound to cancer cells in slices of liver tumor tissues and susceptible human cultured cells and became localized in the plasma membrane until the cells were damaged. Thus, parasporin-2 acts as a cytolysin that permeabilizes the plasma membrane with target cell specificity and subsequently induces cell decay.
authors.affiliation: Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan. s.kitscc@mbox.nc.kyushu-u.ac.jp
authors.forename: Sakae
authors.initials: S
authors.lastname: Kitada
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Abe
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Shimada
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Kusaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Hideki
authors.initials: H
authors.lastname: Katayama
authors.forename: Shiro
authors.initials: S
authors.lastname: Okumura
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Akao
authors.forename: Eiichi
authors.initials: E
authors.lastname: Mizuki
authors.forename: Osamu
authors.initials: O
authors.lastname: Kuge
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.forename: Michio
authors.initials: M
authors.lastname: Ohba
authors.forename: Akio
authors.initials: A
authors.lastname: Ito
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001413:Bacillus thuringiensis / Q000737:chemistry*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D019286:Endopeptidase K / Q000378:metabolism; D004731:Endotoxins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D004731:Endotoxins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C412914:parasporin; C515506:parasporin-2, Bacillus thuringiensis; D019286:Endopeptidase K