Three Cry toxins in two types from Bacillus thuringiensis strain M019 preferentially kill human hepatocyte cancer and uterus cervix cancer cells.
Bacillus thuringiensis strain M019, non-pathogenic to lepidopteran and dipteran insects, produces a parasporal inclusion that consists of three 84-kDa Cry proteins (CPs). CP78A and CP78B, which exhibit 83.5% amino acid identity, were new variants of the previously reported HeLa cell-killing protein (parasporin-1). CP84 was a novel CP showing low-level homology, of 21.9% (56.4% similarity), with the insecticidal Cry2 toxin. In vitro solubilization with dithiothreitol at pH 10.2 and limited hydrolysis with trypsin resulted in the removal of N-terminal portions of the CPs and their activation. The 70-kDa proteins (15- and 55-kDa fragments) from CP78A and CP78B and the 73-kDa protein (14- and 59-kDa fragments) from CP84 exhibited varying degrees of cytocidal activity preferentially toward human hepatocyte cancer HepG2 cells and uterus cervix cancer HeLa cells causing cell swelling or the formation of vacuoles in the cytoplasm. These toxins appeared to attack an identical target on human cells.
Nagamatsu
Yasunori
Y
Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan. nagamats@hiroshima-u.ac.jp
Okamura
Shoutarou
S
Saitou
Hiroyuki
H
Akao
Tetsuyuki
T
Mizuki
Eiichi
E
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001413:Bacillus thuringiensis / Q000378:metabolism*; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000494:pharmacology*; D004229:Dithiothreitol / Q000737:chemistry; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006460:Hemolysin Proteins / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008969:Molecular Sequence Data; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D004731:Endotoxins; D006460:Hemolysin Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis; C412914:parasporin; D004229:Dithiothreitol