title: Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: an in vitro investigation on human breast cancer and leukemia cell lines.
abstract: OBJECTIVE
  Histone modification has emerged as a promising approach to cancer therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD) inhibitor, has shown anticancer activity. Butyrate transcriptional activation is indeed able to withdraw cancer cells from the cell cycle, leading to programmed cell death. Since butyrate's clinical use is hampered by unfavorable pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid lipid nanoparticles (SLN), have been developed to overcome these constraints.
  
  
  METHODS
  In order to outline the influence of butyrate delivery on its anticancer activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth of different human cancer cell lines, such as the promyelocytic leukemia, HL-60, and the breast cancer, MCF-7 was investigated. A detailed investigation into the mechanism of the induced cytotoxicity was also carried out, with a special focus on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by real time PCR analysis.
  
  
  RESULTS
  In HL-60 cells, CBSLN induced a higher and prolonged expression level of the butyrate target genes at lower concentrations than NB. This led to a significant decrease in cell proliferation, along with considerable apoptosis, cell cycle block in the G0/G1 phase, significant inhibition of total HD activity and overexpression of the p21 protein. Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the butyrate target genes, leading to the same anticancer activity as that of NB.
  
  
  CONCLUSIONS
  Solid lipid nanoparticles were able to improve butyrate anticancer activity in HL-60, but not in MCF-7 cells. This is consistent with difference in properties of the cells under study, such as expression of the TP53 tumor suppressor, or the transporter for short-chain fatty acids, SLC5A8.
authors.affiliation: University of Torino.
authors.forename: Federica
authors.initials: F
authors.lastname: Foglietta
authors.forename: Loredana
authors.initials: L
authors.lastname: Serpe
authors.forename: Roberto
authors.initials: R
authors.lastname: Canaparo
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Vivenza
authors.forename: Giovanna
authors.initials: G
authors.lastname: Riccio
authors.forename: Erica
authors.initials: E
authors.lastname: Imbalzano
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasco
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Zara
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002087:Butyrates / Q000008:administration & dosage* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D008055:Lipids