title: In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric acid pro-drug on melanoma cells: evaluation of antiproliferative activity and apoptosis induction.
abstract: Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G(0/1)-S transition block and a 'sub-G(0/1)' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.
authors.affiliation: Department of Medical and Surgical Specialties, University of Turin, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Salomone
authors.forename: R
authors.initials: R
authors.lastname: Ponti
authors.forename: M R
authors.initials: MR
authors.lastname: Gasco
authors.forename: E
authors.initials: E
authors.lastname: Ugazio
authors.forename: P
authors.initials: P
authors.lastname: Quaglino
authors.forename: S
authors.initials: S
authors.lastname: Osella-Abate
authors.forename: M G
authors.initials: MG
authors.lastname: Bernengo
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D020148:Butyric Acid / Q000008:administration & dosage* / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects; D002788:Cholesterol Esters / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006633:Histamine Antagonists / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008081:Liposomes; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D008863:Microspheres; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
chemical_list: D017304:Annexin A5; D002788:Cholesterol Esters; D006633:Histamine Antagonists; D008081:Liposomes; D011355:Prodrugs; D020148:Butyric Acid