Studies on cell growth stimulating substances of low molecular weight. Part 2. Exfoliazone and lavanducyanin, potent growth promoting substances of rat liver cell line, RLN-8, produced by Streptomyces exfoliatus and Streptomyces aeriouvifer.
Exfoliazone and lavanducyanin isolated from Streptomyces exfoliatus BT-38 and Streptomyces aeriouvifer CL-190, respectively, showed strong growth promoting activities to liver cell RLN-8 established from normal Donryu rat. When RLN-8 cells were cultured in Eagle's minimal essential medium containing 1% fetal bovine serum, exfoliazone significantly stimulated the growth of RLN-8 cells. However, no effect was observed under serum-free conditions. Effective dose of exfoliazone was at the range of 0.004-0.1 microgram/ml. Cell proliferation was confirmed by MTT assay and by the increases of cell number and DNA synthesis. Lavanducyanin also stimulated the growth of RLN-8 cells in the same medium. It showed growth promoting activity at lower concentrations than exfoliazone and the effective dose was at the range of 0.0001-0.06 microgram/ml. Analogous compounds of exfoliazone and lavanducyanin also promoted the growth of RLN-8 cells. In addition, exfoliazone and lavanducyanin enhanced the growth of NIH 3T3 and T601 cells. These results indicate that exfoliazone, lavanducyanin and their related compounds seem to be a new type of growth promoting substances with low molecular weight produced by microorganisms, and that they can partially substitute for functions of serum. Since 12-O-tetradecanoylphorbol-13-acetate (TPA) did not show the growth promoting activities under the same conditions, the action mechanism(s) of exfoliazone and lavanducyanin are different from that of TPA.
Imai
S
S
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Noguchi
T
T
Seto
H
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006133:Growth Substances / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D010078:Oxazines / Q000494:pharmacology; D010619:Phenazines / Q000494:pharmacology*; D051381:Rats; D013302:Streptomyces / Q000378:metabolism*
D006133:Growth Substances; D010078:Oxazines; D010619:Phenazines; C060460:lavanducyanin; C067081:exfoliazone