TY - JOUR
T1 - Hyaluronic-acid butyric esters as promising antineoplastic agents in human lung carcinoma
T2 - A preclinical study
AU - Coradini, Danila
AU - Pellizzaro, Cinzia
AU - Abolafio, Gabriella
AU - Bosco, Marco
AU - Scarlata, Ignazio
AU - Cantoni, Silvia
AU - Stucchi, Luca
AU - Zorzet, Sonia
AU - Turrin, Claudia
AU - Sava, Gianni
AU - Perbellini, Alberto
AU - Daidone, Maria Grazia
PY - 2004/8
Y1 - 2004/8
N2 - 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 (p27kip1, 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.
AB - 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 (p27kip1, 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.
KW - Butyric ester
KW - Cell lung carcinoma
KW - Hyaluronic acid
UR - http://www.scopus.com/inward/record.url?scp=3242697385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3242697385&partnerID=8YFLogxK
U2 - 10.1023/B:DRUG.0000026247.72656.8a
DO - 10.1023/B:DRUG.0000026247.72656.8a
M3 - Article
C2 - 15122068
AN - SCOPUS:3242697385
VL - 22
SP - 207
EP - 217
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 3
ER -