A Bacillus thuringiensis crystal protein with selective cytocidal action to human cells.
Bacillus thuringiensis crystal proteins, well known to be toxic to certain insects but not pathogenic to mammals, are used as insecticidal proteins in agriculture and forest management. We here identified a crystal protein that is non-insecticidal and non-hemolytic but has strong cytocidal activity against various human cells with a markedly divergent target specificity, e.g. highly cytotoxic to HepG2 and Jurkat and less cytotoxic to the normal hepatocyte (HC) and HeLa. In slices of liver and colon cancer tissues, the toxin protein preferentially killed the cancer cells, leaving other cells unaffected. The cytocidal effect of the protein is non-apoptotic with swelling and fragmentation of the susceptible cells, although the apoptotic process does occur when the cell damage proceeded slowly. The amino acid sequence deduced from the nucleotide sequence of the cloned gene of the protein has little sequence homology with the insecticidal crystal proteins of B. thuringiensis. These observations raise the presence of a new group of the B. thuringiensis toxin and the possibility of new applications for the protein in the medical field.
Ito
Akio
A
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan. a.itoscc@mbox.nc.kyushu-u.ac.jp
Sasaguri
Yasuyuki
Y
Kitada
Sakae
S
Kusaka
Yoshitomo
Y
Kuwano
Kyoko
K
Masutomi
Kenjiro
K
Mizuki
Eiichi
E
Akao
Tetsuyuki
T
Ohba
Michio
M
D001413:Bacillus thuringiensis / Q000472:pathogenicity; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000633:toxicity*; D001427:Bacterial Toxins; D002118:Calcium / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004731:Endotoxins / Q000633:toxicity*; D006367:HeLa Cells; D006460:Hemolysin Proteins; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000187:drug effects*
D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004731:Endotoxins; D006460:Hemolysin Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis; C412914:parasporin; D002118:Calcium