In vivo antitumor activity of clitocine, an exocyclic amino nucleoside isolated from Lepista inversa.
A biologically guided fractionation from Lepista inversa (Scop.: Fr.) led to the isolation of clitocine, an exocyclic amino nucleoside. This compound and two mixtures of beta/alpha anomers (mixture A, 40:60 and mixture B, 80:20) were synthesized or isolated depending on the purification procedure. The beta anomer and clitocine mixtures A and B showed similar cytotoxic activities with IC50 values ranging from 20.5 to 42 nM in murine cancer cell lines (3LL and L1210) and from 185 to 578 nM in human cancer cell lines (DU145, K-562, MCF7, and U251). An in vivo study of mixture B was carried out on 3LL- and L1210-tumor-bearing mice. Clitocine solubilized in beta-hydroxypropylcyclodextrin and injected at concentrations of 0.5, 3, and 5 mg kg-1 did not significantly increase the survival rate and lifespan of 3LL-tumor-bearing mice. In contrast, clitocine showed antitumor activity on L1210-tumor-bearing mice with a significant increase in lifespan and a decrease in the development of ascites observed at 3 mg kg-1. The induction of apoptosis may be the basis of the antitumor activity of clitocine against L1210 as suggested by flow-cytometry analysis of cells treated in vitro.
Fortin
Hélène
H
Institut de Chimie de Rennes, Laboratoire de Pharmacognosie et de Mycologie, EA Substances Lichéniques et Photoprotection, Faculté de Pharmacie, Université Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes Cedex, France.
Tomasi
Sophie
S
Delcros
Jean-Guy
JG
Bansard
Jean-Yves
JY
Boustie
Joël
J
D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011741:Pyrimidine Nucleosides / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011741:Pyrimidine Nucleosides; C055433:clitocine