Cytocidal actions of parasporin-2, an anti-tumor crystal toxin from Bacillus thuringiensis

Sakae Kitada, Yuichi Abe, Hiroyasu Shimada, Yoshitomo Kusaka, Yoko Matsuo, Hideki Katayama, Shiro Okumura, Tetsuyuki Akao, Eiichi Mizuki, Osamu Kuge, Yasuyuki Sasaguri, Michio Ohba, Akio Ito

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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.

Original languageEnglish
Pages (from-to)26350-26360
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number36
DOIs
Publication statusPublished - Sep 8 2006

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kitada, S., Abe, Y., Shimada, H., Kusaka, Y., Matsuo, Y., Katayama, H., ... Ito, A. (2006). Cytocidal actions of parasporin-2, an anti-tumor crystal toxin from Bacillus thuringiensis. Journal of Biological Chemistry, 281(36), 26350-26360. https://doi.org/10.1074/jbc.M602589200