Unique activity associated with non-insecticidal Bacillus thuringiensis parasporal inclusions: in vitro cell-killing action on human cancer cells.
Parasporal inclusion proteins from a total of 1744 Bacillus thuringiensis strains, consisting of 1700 Japanese isolates and 44 reference type strains of existing H serovars, were screened for cytocidal activity against human leukaemia T cells and haemolytic activity against sheep erythrocytes. Of 1684 B. thuringiensis strains having no haemolytic activity, 42 exhibited in vitro cytotoxicity against leukaemia T cells. These non-haemolytic but leukaemia cell-toxic strains belonged to several H-serovars including dakota, neoleonensis, shandongiensis, coreanensis and other unidentified serogroups. Purified parasporal inclusions of the three selected strains, designated 84-HS-1-11, 89-T-26-17 and 90-F-45-14, exhibited no haemolytic activity and no insecticidal activity against dipteran and lepidopteran insects, but were highly cytocidal against leukaemia T cells and other human cancer cells, showing different toxicity spectra and varied activity levels. Furthermore, the proteins from 84-HS-1-11 and 89-T-26-17 were able to discriminate between leukaemia and normal T cells, specifically killing the former cells. These findings may lead to the use of B. thuringiensis inclusion proteins for medical purposes.
Mizuki
E
E
Biotechnology & Food Research Institute, Fukuoka Industrial Technology Centre, Kurume, Japan. emizuki@bfri01.fitc.pref.fukuoka.jp
Ohba
M
M
Akao
T
T
Yamashita
S
S
Saitoh
H
H
Park
Y S
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001413:Bacillus thuringiensis / Q000737:chemistry*; D001426:Bacterial Proteins / Q000032:analysis / Q000494:pharmacology*; D012831:Bombyx / Q000187:drug effects; D003058:Cockroaches / Q000187:drug effects; D004175:Diptera / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007306:Insecticides / Q000494:pharmacology; D020049:Isoptera / Q000187:drug effects; D015458:Leukemia, T-Cell; D008175:Lung Neoplasms; D009987:Orthoptera / Q000187:drug effects; D013171:Spores, Bacterial / Q000737:chemistry*
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D007306:Insecticides