title: Induction of apoptosis in human cancer cells by a Bacillus lipopeptide bacillomycin D.
abstract: A newly isolated and characterized Bacillus amyloliquefaciens strain fiply 3A has been found to produce an extracellular cyclic lipopeptide which structurally resembled bacillomycin D, earlier reported to be produced by Bacillus subtilis. The lipopeptide showed a dose dependent killing of three different human cancer cell lines viz. A549 (alveolar adenocarcinoma), A498 (renal carcinoma) and HCT-15 (colon adenocarcinoma), while not affecting the normal cell line L-132 (pulmonary epithelial cells) when analyzed using MTT assay and FACS analysis. Staining the cells with H2-DCFDA showed an increase in reactive oxygen species (ROS) formation in the lipopeptide treated cell population. Hoechst 33342 staining of nuclei further indicated apoptosis as a major mechanism of cell death in lipopeptide treated cells and the typical symptoms of apoptosis including cell shrinkage, nuclear condensation and fragmentation of nuclei were observed. Lipopeptide treatment induced extensive DNA damage in the treated cells, which was indicated by a TUNEL assay. Flow cytometric analysis exhibited lipopeptide concentration dependent apoptosis which was further confirmed during clonogenic assay of the lipopeptide treated cells.
authors.affiliation: Food Technology Division, FIPLY, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Sachin N
authors.initials: SN
authors.lastname: Hajare
authors.forename: Mahesh
authors.initials: M
authors.lastname: Subramanian
authors.forename: Satyendra
authors.initials: S
authors.lastname: Gautam
authors.forename: Arun
authors.initials: A
authors.lastname: Sharma
mesh_terms: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001407:Bacillus / Q000737:chemistry*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D016193:G1 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
chemical_list: C494829:AIFM1 protein, human; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D055666:Lipopeptides; D010455:Peptides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C027845:bacillomycin D; D045304:Cytochromes c; D020169:Caspases
keywords: Anticancer; Apoptosis; Bacillomycin D; Bacillus; Lipopeptide; ROS