Typical three-domain cry proteins of Bacillus thuringiensis strain A1462 exhibit cytocidal activity on limited human cancer cells.
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.
Yamashita
Satoko
S
Biotechnology & Food Research Institute, Fukuoka Industrial Technology Center, Fukuoka. syamashi@fitc.pref.fukuoka.jp
Katayama
Hideki
H
Saitoh
Hiroyuki
H
Akao
Tetsuyuki
T
Park
Yu Shin
YS
Mizuki
Eiichi
E
Ohba
Michio
M
Ito
Akio
A
D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D001413:Bacillus thuringiensis / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005798:Genes, Bacterial; D006801:Humans; D019476:Insect Proteins; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; C095416:Cry toxin receptors; D019476:Insect Proteins; D011956:Receptors, Cell Surface