title: Cholesteryl butyrate solid lipid nanoparticles as a butyric acid pro-drug: effects on cell proliferation, cell-cycle distribution and c-myc expression in human leukemic cells.
abstract: Cholesteryl butyrate solid lipid nanoparticles (chol-but SLN) have been proposed as a pro-drug to deliver butyric acid. We compared the effects on cell growth, cell-cycle distribution and c-myc expression of chol-but SLN and sodium butyrate (Na-but) in the human leukemic cell lines Jurkat, U937 and HL-60. In all the cell lines 0.5 and 1.0 mM chol-but SLN provoked a complete block of cell growth. Cell-cycle analysis demonstrated in Jurkat cells that 0.25 mM chol-but SLN caused a pronounced increase of G2/M cells and a decrease of G0/G1 cells, whereas in U937 and HL-60 cells chol-but SLN led to a dose-dependent increase of G0/G1 cells, with a decrease of G2/M cells. In Jurkat and HL-60 cells 0.5 mM chol-but SLN induced a significant increase of sub-G0/G1 apoptotic cells. Cell growth and cell-cycle distribution were unaffected by the same concentrations of Na-but. A concentration of 0.25 mM chol-but SLN was able to cause a rapid and transient down-regulation of c-myc expression in all the cell lines, whereas 1 mM Na-but caused a slight reduction of c-myc expression only in U937 cells. The results show how chol-but SLN affects the proliferation pattern of both myeloid and lymphoid cells to an extent greater than the natural butyrate.
authors.affiliation: Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy. loredana.serpe@unito.it
authors.forename: Loredana
authors.initials: L
authors.lastname: Serpe
authors.forename: Stefano
authors.initials: S
authors.lastname: Laurora
authors.forename: Stefania
authors.initials: S
authors.lastname: Pizzimenti
authors.forename: Elena
authors.initials: E
authors.lastname: Ugazio
authors.forename: Renata
authors.initials: R
authors.lastname: Ponti
authors.forename: Roberto
authors.initials: R
authors.lastname: Canaparo
authors.forename: Federica
authors.initials: F
authors.lastname: Briatore
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barrera
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Gasco
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bernengo
authors.forename: Mario
authors.initials: M
authors.lastname: Eandi
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Zara
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002087:Butyrates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002788:Cholesterol Esters / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008856:Microscopy, Fluorescence; D036103:Nanotechnology; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D011355:Prodrugs / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D020298:U937 Cells
chemical_list: D002087:Butyrates; D002788:Cholesterol Esters; C489427:MYC protein, human; D010713:Phosphatidylcholines; D011355:Prodrugs; D016271:Proto-Oncogene Proteins c-myc