Calcium Signaling of Dioleoyl Phosphatidic Acid via Endogenous LPA Receptors: A Study Using HCT116 and HT29 Human Colon Cancer Cell Lines

In the present study, we have tested the effect of dioleoyl phosphatidic acid (PA) on intracellular concentration () in two human colon cancer cell lines (HCT116 and HT29). PA and lysophosphatidic acid (LPA), a bioactive lysolipid, increased in both HCT116 and HT29 cell lines. Increases of by PA and LPA were more robust in HCT116 cells than in HT29 cells. A specific inhibitor of phospholipase C (U73122), however, was not inhibitory to the cell responses. Pertussis toxin, a specific inhibitor of type G proteins, however, had an inhibitory effect on the responses except for an LPA-induced one in HT29 cells. Ruthenium red, an inhibitor of the ryanodine receptor, was not inhibitory on the responses, however, 2-APB, a specific inhibitor of inositol 1,4,5-trisphosphate receptor, completely inhibited both lipid-induced increases in both cell types. Furthermore, by using Ki16425 and VPC32183, two structurally dissimilar specific antagonists for receptors, an involvement of endogenous LPA receptors in the responses was observed. Ki16425 completely inhibited the responses but the susceptibility to VPC32183 was different to PA and LPA in the two cell types. Expression levels of five LPA receptors in the HCT116 and HT29 cells were also assessed. Our data support the notion that PA could increase in human colon cancer cells, probably via endogenous LPA receptors, G proteins and receptors, thereby suggesting a role of PA as an intercellular lipid mediator.