Parasporin-2 from a New Bacillus thuringiensis 4R2 Strain Induces Caspases Activation and Apoptosis in Human Cancer Cells.
In previous studies, parasporin-2Aa1, originally isolated from Bacillus thuringiensis strain A1547, was shown to be cytotoxic against specific human cancer cells but the mechanisms of action were not studied. In the present study, we found that proteinase K activated parasporin-2Aa1 protein isolated from a novel B. thuringiensis strain, 4R2, was specifically cytotoxic to endometrial, colon, liver, cervix, breast and prostate cancer. It showed no toxicity against normal cells. Upon treatment with proteinase K-activated parasporin-2Aa1, morphological changes were observed and western blot analysis revealed the cleavage of poly (ADP-Ribose) polymerase, caspase-3 and caspase-9 in cancer cell lines exclusively, indicative of programmed cell death, apoptosis. Flow cytometry analyses,using propidium iodide and annexin V, as well as a caspases 3/7 assay confirmed apoptosis induction. Further analyses were performed to study survival pathways, including AKT, XIAP, ERK1/2 and PAR-4, a known inducer of apoptosis. These results indicate that parasporin-2Aa1 is a selective cytotoxic protein that induces apoptosis in various human cancer cell lines from diverse tissues.
Research Group in Molecular Oncology and Endocrinology, Department of Medical Biology, Université du Québec à Trois-Rivières, 3351, Boul. Des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7.
Kevin
K
Brasseur
Research Group in Molecular Oncology and Endocrinology, Department of Medical Biology, Université du Québec à Trois-Rivières, 3351, Boul. Des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7.
Pascal
P
Auger
Research Group in Molecular Oncology and Endocrinology, Department of Medical Biology, Université du Québec à Trois-Rivières, 3351, Boul. Des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7.
Eric
E
Asselin
Research Group in Molecular Oncology and Endocrinology, Department of Medical Biology, Université du Québec à Trois-Rivières, 3351, Boul. Des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7.
Sophie
S
Parent
Agriculture and Agri-Food Canada, Research Centre, 430, Boul. Gouin, Saint-Jean-sur-Richelieu, Québec, Canada J3B 3E6.
Jean-Charles
JC
Côté
Research Group in Molecular Oncology and Endocrinology, Department of Medical Biology, Université du Québec à Trois-Rivières, 3351, Boul. Des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7.
Marc
M
Sirois
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D001413:Bacillus thuringiensis / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004731:Endotoxins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D004731:Endotoxins; C412914:parasporin; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases