Ito Akio, Sasaguri Yasuyuki, Kitada Sakae, Kusaka Yoshitomo, Kuwano Kyoko, Masutomi Kenjiro, Mizuki Eiichi, Akao Tetsuyuki, Ohba Michio
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan.
J Biol Chem. 2004 May 14;279(20):21282-6. doi: 10.1074/jbc.M401881200. Epub 2004 Mar 16.
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.
苏云金芽孢杆菌晶体蛋白对某些昆虫有毒，但对哺乳动物无致病性，在农业和森林管理中用作杀虫蛋白。我们在此鉴定出一种晶体蛋白，它无杀虫活性且无溶血活性，但对各种人类细胞具有强大的杀细胞活性，其靶标特异性明显不同，例如对HepG2和Jurkat细胞具有高度细胞毒性，而对正常肝细胞（HC）和HeLa细胞的细胞毒性较小。在肝癌和结肠癌组织切片中，该毒素蛋白优先杀死癌细胞，而其他细胞不受影响。该蛋白的杀细胞作用是非凋亡性的，易感细胞会肿胀和破碎，不过当细胞损伤进展缓慢时，凋亡过程确实会发生。从该蛋白克隆基因的核苷酸序列推导的氨基酸序列与苏云金芽孢杆菌的杀虫晶体蛋白几乎没有序列同源性。这些观察结果提示存在一类新的苏云金芽孢杆菌毒素，以及该蛋白在医学领域新应用的可能性。
