title: Nanocytotoxicity: violacein and violacein-loaded poly (D, L-lactide-co-glycolide) nanoparticles acting on human leukemic cells.
abstract: Violacein is a compound obtained from Chromobacterium violaceum, a bacterium found in the Amazonian region. Violacein-loaded poly (D, L-lactide-co-glycolide) nanoparticles has a similar inhibitory effect evaluated by trypan blue assay on leukemic HL60 cells than the free form. However, the cytotoxic effects evaluated by phosphatase activity and MTT reduction assays were lower for the encapsulated form than for free violacein. Based on morphological changes, violacein and violacein entrapped in nanoparticles were found to induce terminal differentiation (assessed by nitro blue tetrazolium reduction) in HL60 cells. Thus, both formulations inhibit HL60 cell growth in vitro, partly by inducing cytotoxic effects and cell differentiation. Flow cytometric analysis of HL60 cells after treatment for 12 h showed that violacein-loaded PLGA induced apoptosis, with maximum cell death at a concentration of 2 microM. Violacein and violacein/PLGA induced opposite effects on the mitochondrial swelling which indicates altered mitochondrial function. The mitochondrial activity was also checked by flow cytometry studies. Labelled cells with the probe JC1 displayed a basal hypopolarized status of the mitochondria in treated cells. Based on morphological changes, alterations in phospholipid asymmetry and changes in mitochondrial polarization, violacein and nanoparticles containing violacein were found to trigger cell death by apoptosis. These methodologies are promising as diagnostic and mechanistic effects of nanoparticles in cell cultures.
authors.affiliation: Biochemistry Department, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, Campinas, SP, 13083-970, Brazil.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Melo
authors.forename: Marcelo M M
authors.initials: MM
authors.lastname: De Azevedo
authors.forename: Lucas
authors.initials: L
authors.lastname: Frungillo
authors.forename: Maristela C
authors.initials: MC
authors.lastname: Anazetti
authors.forename: Priscyla D
authors.initials: PD
authors.lastname: Marcato
authors.forename: Nelson
authors.initials: N
authors.lastname: Duran
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D003460:Crystallization / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D007211:Indoles; D046911:Macromolecular Substances; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C063155:violacein