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Solid lipid nanoparticles of cholesteryl butyrate inhibit the proliferation of cancer cells in vitro and in vivo models
Author(s) -
Minelli R,
Occhipinti S,
Gigliotti C L,
Barrera G,
Gasco P,
Conti L,
Chiocchetti A,
Zara G P,
Fantozzi R,
Giovarelli M,
Dianzani U,
Dianzani C
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12255
Subject(s) - in vivo , clonogenic assay , butyrate , cell growth , cell culture , viability assay , in vitro , cell cycle , cancer cell , chemistry , solid lipid nanoparticle , cancer research , biology , cell , microbiology and biotechnology , pharmacology , cancer , biochemistry , drug , genetics , fermentation
Background and Purpose Solid lipid nanoparticles containing cholesteryl butyrate (cholbut SLN ) can be a delivery system for the anti‐cancer drug butyrate. These nanoparticles inhibit adhesion of polymorphonuclear and tumour cells to endothelial cells and migration of tumour cells, suggesting that they may act as anti‐inflammatory and anti‐tumour agents. Here we have evaluated the effects of cholbut SLN on tumour cell growth using in vitro and in vivo models. Experimental Approach Cholbut SLN s were incubated with cultures of four tumour cell lines, and cell growth was analysed by assessing viability, clonogenic capacity and cell cycle. Effects on intracellular signalling was assessed by W estern blot analysis of A kt expression. The in vivo anti‐tumour activity was measured in two models of PC ‐3 cell xenografts in SCID /Beige mice. Key Results Cholbut SLN inhibited tumour cell line viability, clonogenic activity, A kt phosphorylation and cell cycle progression. In mice injected i.v. with PC3 ‐ L uc cells and treated with cholbut SLN, . in vivo optical imaging and histological analysis showed no metastases in the lungs of the treated mice. In another set of mice injected s.c. with PC ‐3 cells and treated with cholbut SLN when the tumour diameter reached 2 mm, analysis of the tumour dimensions showed that treatment with cholbut SLN substantially delayed tumour growth. Conclusion and Implications Cholbut SLN were effective in inhibiting tumour growth in vitro and in vivo . These effects may involve, in part, inhibition of A kt phosphorylation, which adds another mechanism to the activity of this multipotent drug.