Selective cytotoxic activity against leukemic cell lines from mosquitocidal Bacillus thuringiensis parasporal inclusions.

ABSTRACT

The discovery of parasporin has triggered an interest in examining various Bacillus thuringiensis (Bt) isolates for specific anti-cancer activity. The aim of this study was to determine the potency and specificity of parasporal inclusions from Malaysian mosquitocidal Bt isolates against a leukemic cell line (CEM-SS). The Bt isolates used in this study were identified as having weak to potent larvicidal activity against Aedes aegypti and varying hemolytic activity. The 12 mosquitocidal Bt isolates examined in this study showed low to moderate cytotoxicity when tested against CEM-SS and HeLa. Interestingly the parasporal inclusions of Bt 18 (non-hemolytic isolate), showed therapeutic potential demonstrating specificity for CEM-SS compared to HeLa, whilst being non-cytotoxic to normal T lymphocytes. The mode of cell death by Bt 18 was shown to be initially apoptotic. SDS-PAGE analysis and N-terminal sequencing of the upper and lower bands of Bt 18 showed similarity between Bt 18 parasporal inclusions with Cry 24Aa and 25Aa of Bacillus thuringiensis subsp jegathesan and Cry 15Aa of Bacillus thuringiensis subsp israelensis. Although the BLAST analysis did not show sequence similarity between Bt 18 and Parasporin, we propose that the Bt 18 parasporal inclusions share similar characteristics to Parasporin since Bt 18 is not hemolytic but discriminately cytotoxic towards leukemic cell lines.