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A Bacillus thuringiensis crystal protein with selective cytocidal action to human cells
Akio Ito1, Yasuyuki Sasaguri, Sakae Kitada
1Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan. a.itoscc@mbox.nc.kyushu-u.ac.jp
The Journal of Biological Chemistry
|March 18, 2004
Summary
Researchers discovered a new Bacillus thuringiensis crystal protein. This non-insecticidal protein shows potent cytocidal activity against human cancer cells, suggesting novel medical applications.
Area of Science:
- Microbiology
- Biochemistry
- Cell Biology
Background:
- Bacillus thuringiensis (Bt) crystal proteins are widely used as biopesticides due to their insecticidal properties and safety to mammals.
- The specific mechanisms and target range of Bt toxins are crucial for understanding their applications and potential limitations.
Purpose of the Study:
- To identify and characterize novel Bt crystal proteins with unique biological activities.
- To investigate the cytocidal effects of a newly identified Bt crystal protein on human cell lines and cancer tissues.
- To explore the potential of this novel protein for therapeutic applications.
Main Methods:
- Gene cloning and nucleotide sequencing of the novel Bt crystal protein.
- In vitro cytotoxicity assays using various human cell lines (HepG2, Jurkat, HC, HeLa).
- Ex vivo analysis of the protein's effect on human liver and colon cancer tissue slices.
- Microscopic examination to determine the mode of cell death (cytocidal, apoptotic).
- Amino acid sequence homology analysis compared to known Bt insecticidal proteins.
Main Results:
- A novel Bt crystal protein was identified with significant cytocidal activity against human cancer cell lines (HepG2, Jurkat) but lower toxicity to normal cells (HC, HeLa).
- The protein demonstrated preferential killing of cancer cells within liver and colon cancer tissue samples.
- The primary mode of cell death induced by the protein was non-apoptotic, characterized by cell swelling and fragmentation, though apoptosis was observed under slower damage progression.
- Sequence analysis revealed minimal homology to known insecticidal Bt crystal proteins, indicating a distinct toxin group.
Conclusions:
- A new class of Bacillus thuringiensis toxin with selective cytocidal activity against human cancer cells has been discovered.
- This novel protein exhibits a unique non-apoptotic cell death mechanism.
- The findings suggest promising potential for developing new cancer therapeutics based on this distinct Bt toxin.