title: Hyaluronic-acid butyric esters as promising antineoplastic agents in human lung carcinoma: a preclinical study.
abstract: New promising compounds, derived from the esterification of hyaluronic acid with butyric acid, were investigated in vitro on a non-small cell lung carcinoma cell line (NCI-H460) and an its metastatic subclone (NCI-H460M). All new compounds exerted a dose-dependent inhibitory effect on both cell lines, which expressed CD44, the specific surface receptor for hyaluronic acid, in a very high percentage of cells (90%). HE1, the most effective of these compounds, was 10-fold more effective than sodium butyrate (NaB) in inhibiting cell proliferation. Similarly to NaB, after 24 hours of treatment, HE1 affected the expression of three cell cycle-related proteins (p27(kip1), p53 and p21(waf1)) responsible for growth arrest, indicating that the presence of the hyaluronic acid backbone does not interfere with the biologic activity. Intratumoral treatment with HE1 demonstrated a marked efficacy on primary tumor growth and on lung metastases formation of the murine Lewis Lung Carcinoma model. Altogether, present findings suggest a possible clinical application of these novel butyric pro-drugs in primary and metastatic lung cancer.
authors.affiliation: Unit of Biomolecular Determinants in Prognosis and Therapy, Experimental Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy. danila.coradini@istitutotumori.mi.it
authors.forename: Danila
authors.initials: D
authors.lastname: Coradini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Pellizzaro
authors.forename: Gabriella
authors.initials: G
authors.lastname: Abolafio
authors.forename: Marco
authors.initials: M
authors.lastname: Bosco
authors.forename: Ignazio
authors.initials: I
authors.lastname: Scarlata
authors.forename: Silvia
authors.initials: S
authors.lastname: Cantoni
authors.forename: Luca
authors.initials: L
authors.lastname: Stucchi
authors.forename: Sonia
authors.initials: S
authors.lastname: Zorzet
authors.forename: Claudia
authors.initials: C
authors.lastname: Turrin
authors.forename: Gianni
authors.initials: G
authors.lastname: Sava
authors.forename: Alberto
authors.initials: A
authors.lastname: Perbellini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000556:secondary; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D002087:Butyrates; D004952:Esters; D006820:Hyaluronic Acid