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In Vivo Antitumor Activity of Clitocine, an Exocyclic Amino Nucleoside Isolated from Lepista inversa
Author(s) -
Fortin Hélène,
Tomasi Sophie,
Delcros JeanGuy,
Bansard JeanYves,
Boustie Joël
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200500029
Subject(s) - in vivo , du145 , l1210 cells , nucleoside , flow cytometry , in vitro , chemistry , apoptosis , cell culture , microbiology and biotechnology , cytotoxicity , nucleoside analogue , ehrlich ascites carcinoma , biochemistry , cancer cell , biology , cancer , lncap , genetics
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 β/α anomers (mixture A, 40:60 and mixture B, 80:20) were synthesized or isolated depending on the purification procedure. The β anomer and clitocine mixtures A and B showed similar cytotoxic activities with IC 50 values ranging from 20.5 to 42 n M in murine cancer cell lines (3LL and L1210) and from 185 to 578 n M 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 β‐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.