Role of Alkylglycerol as a Novel Mediator of Density-Dependent Growth Inhibition in Swiss 3T3 Fibroblasts
Document Type
Article
Publication Date
12-1-1997
Description
Inhibition of cell proliferation al a critical cell density is a characteristit feature of normal coils in culture that is lost in many tumor cells. Protein kinase C plays AH important role in the regulation of cell proliferation and is down-regulated in fibroblasts that are growth arrested at a high density. We previously identified alkylglycerol (AG) as a novel endogenous inhibitor of PKCo in MDCK cells. In this study, we investigated the role of AG as a density-dependent inhibitor of cell proliferation in Swiss 3T3 fibroblasts. ACT levels were 46 pmol/106 cells in sparse 3T3 cell cultures and increased to 418 prnol/106 at confluence. We tested the ability of a synthetic, cell-permeable AG, dodecylglycerol (C12-AG), to inhibit 3T3 coll proliferation. Addition of 10μM C12-AG to the growth medium of sparse, proliferating cultures signif icantlv inhibited DNA svnthesis within 12 hours and reduced cell division within 24 hours without toxic effects. Cells grown in the presence of 10μM C12-AG achieved a saturation density that was 30% lower than control cells. Treatment of quiescent fthroblasts cultures with C12- AG potently inhibited mitogenic induction by phorbol ester but not in response to insulin. Thus. AG appears to inhibit cell proliferation through its ability to inhibit PKC. The accumulation of AG during cell-cell contact of fibroblasts and its potent an tiproliferative properties support a role for the compound as a novel mediator of contact inhibition of cell growth. Supported by NIH CA-59981.
Citation Information
Gregory Burnanan, F.; and Robinson, Mitchell. 1997. Role of Alkylglycerol as a Novel Mediator of Density-Dependent Growth Inhibition in Swiss 3T3 Fibroblasts. FASEB Journal. Vol.11(9). ISSN: 0892-6638