A parasporin from Bacillus thuringiensis native to Peninsular India induces apoptosis in cancer cells through intrinsic pathway
| Autor: | Thomas Chubicka, Sasidharan Salini, Thekkekara Devassy Babu, K. Deepa, Menon Kunnathully Divya, Nair Meera, D. Girija, Achuthan C. Raghavamenon |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteolysis 030106 microbiology Bacillus thuringiensis India Antineoplastic Agents Apoptosis Peptide Caspase 3 Biology General Biochemistry Genetics and Molecular Biology HeLa 03 medical and health sciences Neoplasms medicine Humans Cytotoxic T cell chemistry.chemical_classification medicine.diagnostic_test General Medicine biology.organism_classification Molecular biology Endotoxins 030104 developmental biology chemistry Cancer cell General Agricultural and Biological Sciences HeLa Cells |
| Zdroj: | Journal of Biosciences. 43:407-416 |
| ISSN: | 0973-7138 0250-5991 |
| DOI: | 10.1007/s12038-018-9759-0 |
| Popis: | Parasporins, a class of non-insecticidal crystal proteins of Bacillus thuringiensis (Bt) are being explored as promising anticancer agents due to their specific toxicity to cancer cells. The present study has identified 25 Bt isolates harbouring parasporin genes from Western Ghats region, the hotspot of biodiversity in India. Among these, the isolate, KAU 41 (Kerala Agricultural University isolate 41) contained non-hemolytic homogenous crystals showing specific cytotoxicity towards cancer cells. SDS-PAGE analysis of this crystal, isolated by aqueous biphasic separation, revealed a 31 kDa sized peptide. The N-terminal sequence deciphered in BLAST analysis showed homology to a hypothetical Bt protein. Upon proteolysis, a 29 kDa active peptide was generated which exhibited heterogenic cytotoxic spectrum on various cancer cells. HeLa cells were highly susceptible to this peptide with IC 50 1 lg/mL and showed characteristics of apoptosis. RT-qPCR analysis revealed the overexpression of APAF1, caspase 3 and 9 by 14.9, 8 and 7.4 fold, respectively which indicates the activation of intrinsic pathway of apoptosis. However, at higher concentrations of peptide (greater than 3 lg/mL), necrotic death was prominent. The results suggest that the 31 kDa protein from Bt isolate, KAU 41 is a parasporin that may have high therapeutic potential. |
| Databáze: | OpenAIRE |
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