Hyaluronic-acid butyric esters as promising antineoplastic agents in human lung carcinoma: a preclinical study.
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.
Coradini
Danila
D
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
Pellizzaro
Cinzia
C
Abolafio
Gabriella
G
Bosco
Marco
M
Scarlata
Ignazio
I
Cantoni
Silvia
S
Stucchi
Luca
L
Zorzet
Sonia
S
Turrin
Claudia
C
Sava
Gianni
G
Perbellini
Alberto
A
Daidone
Maria Grazia
MG
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
D000970:Antineoplastic Agents; D002087:Butyrates; D004952:Esters; D006820:Hyaluronic Acid