Inhibition of Cell Proliferation by a Unique Lysophosphatidic Acid, PHYLPA, Isolated from Physarum polycephalum: Signaling Events of Antiproliferative Action by PHYLPA

Abstract

The unique Physarum lysophosphatidic acid, PHYLPA, having a cyclopropane in the fatty acid moiety and a cyclic phosphate at C-2 and C-3 positions of the glycerol (16), inhibited proliferation of human fibroblast cells, TIG-3 and TIG-7, which were cultured in a chemically defined (serum-free) medium. The cells at S- and M-phases proceeded to G₂- and G₁-phases, respectively, and most of cells were arrested at G₁- or G₂- phase during PHYLPA treatment. The growth was recovered when PHYLPA was removed from the medium. In the presence of serum, PHYLPA did not show obvious inhibitory effects, indicating the existence of a factor(s) which neutralizes the antiproliferative activity of PHYLPA.
PHYLPA elicited an increase in 3', 5' -cyclic adenosine monophosphate (cAMP) in a biphasic fashion in fibroblast cells. It also elicited inositol phosphate accumulation, as well as a transient rise in cytoplasmic free Ca²⁺ ion.