Total structure and inhibition of tumor cell proliferation of laxaphycins.
From a mixed assemblage of Lyngbya majuscula rich marine cyanobacteria, we isolated a series of cell growth inhibitory cyclic peptides. The structures of the two major components, laxaphycins A (1) and B (2), and of two minor peptides, laxaphycins B2 (3) and B3 (4), were determined by spectroscopic methods and degradative analysis. Absolute configurations of natural and nonproteinogenic amino acids were determined by a combination of hydrolysis, synthesis of noncommercial residues, chemical derivatization, and HPLC analysis. The organism producing the laxaphycins was identified as the cyanobacterium Anabaena torulosa. The antiproliferative activity of laxaphycins was investigated on a panel of solid and lymphoblastic cancer cells. Our results demonstrate that in contrast to laxaphycin A, laxaphycin B inhibits the proliferation of sensitive and resistant human cancer cell lines and that this activity is strongly increased in the presence of laxaphycin A. This effect appears to be due to an unusual biological synergism.
Bonnard
Isabelle
I
Laboratoire de Chimie des Biomolécules et de l'Environnement, Université de Perpignan Via Domitia, 66860 Perpignan, France.
Rolland
Marc
M
Salmon
Jean-Marie
JM
Debiton
Eric
E
Barthomeuf
Chantal
C
Banaigs
Bernard
B
D017033:Anabaena / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; C503383:Laxaphycin A; C503384:Laxaphycin B; D010456:Peptides, Cyclic; C519099:laxaphycin B2; C519100:laxaphycin B3