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Journal of Biochemistry 2005 138(6):663-672; doi:10.1093/jb/mvi177
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© 2005 The Japanese Biochemical Society.

Regular Paper

Typical Three-Domain Cry Proteins of Bacillus thuringiensis Strain A1462 Exhibit Cytocidal Activity on Limited Human Cancer Cells

Satoko Yamashita1,2,*, Hideki Katayama1, Hiroyuki Saitoh1, Tetsuyuki Akao1, Yu Shin Park1,{dagger}, Eiichi Mizuki1, Michio Ohba3 and Akio Ito2

1 Biotechnology & Food Research Institute, Fukuoka Industrial Technology Center, Fukuoka 839-0861; and 2 Department of Chemistry, Faculty of Science, and 3 Graduate School of Agriculture, Kyushu University, Fukuoka 812-8581

* To whom correspondence should be addressed at: Biotechnology & Food Research Institute, Fukuoka Industrial Technology Center, Aikawa-machi 1465-5, Kurume, Fukuoka 839-0861. Tel: +81-942-30-6644, Fax: +81-942-30-7244, E-mail: syamashi{at}fitc.pref.fukuoka.jp

Bacillus thuringiensis strain A1462 produced two parasporal inclusion proteins with a molecular mass of 88 kDa that were converted to 64-kDa toxins when activated by proteinase K digestion. Both toxins exhibited strong cytocidal activity against two human cancer cell lines, HL60 (myeloid leukemia cells) and HepG2 (liver cancer cells), while low or no toxicities were observed against 11 human and three mammalian cell lines, including four non-cancer cell lines. The cytotoxicity of both toxins on susceptible cells was characterized by rapid cell swelling. Gene cloning experiments provided two novel genes encoding 88-kDa Cry proteins, Cry41Aa and Cry41Ab. The amino acid sequences of the two proteins contain five block regions commonly conserved in B. thuringiensis insecticidal Cry proteins. This is the first report of the occurrence of typical three-domain Cry proteins with cytocidal activity preferential for cancer cells.

{dagger} Present address: Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea.


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