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Byline: Danila Coradini (1), Cinzia Pellizzaro (1), Gabriella Abolafio (1), Marco Bosco (2), Ignazio Scarlata (3), Silvia Cantoni (3), Luca Stucchi (2), Sonia Zorzet (4), Claudia Turrin (4,5), Gianni Sava (4,5), Alberto Perbellini (6), Maria Grazia Daidone (1) Keywords: hyaluronic acid; butyric ester; cell lung carcinoma 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.sup.kip1, p53 and p21.sup.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. Author Affiliation: (1) Unit of Biomolecular Determinants in Prognosis and Therapy, Experimental Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (2) POLYtech, Area di Ricerca, Padriciano 99, Trieste (3) BBCM Department, University of Trieste, Italy (4) Department of Biomedical Science, University of Trieste, Italy (5) Callerio Foundation, Via Fleming 22, Trieste (6) Coimex S.c.r.l., Via P. Borsellino 2, Reggio Emilia, Italy Article History: Registration Date: 21/10/2004