Mitogenic action of lysophosphatidic acid and phosphatidic acid on fibroblasts. Dependence on acyl-chain length and inhibition by suramin

Biochem J. 1992 Jan 1;281 ( Pt 1)(Pt 1):163-9. doi: 10.1042/bj2810163.


Lysophosphatidic acid (LPA) is a naturally occurring phospholipid with growth-factor-like activities [van Corven, Groenink, Jalink, Eichholtz & Moolenaar (1989) Cell 45, 45-54]. We have examined various structural analogues of LPA for their ability to stimulate DNA synthesis in quiescent fibroblasts. When the acyl-chain length is varied, the rank order of mitogenic potency is: 1-oleoyl LPA congruent to 1-palmitoyl LPA greater than 1-myristoyl LPA greater than 1-lauroyl LPA greater than 1-decanoyl LPA; the last compound shows almost no activity over the concentration range tested (1-100 microM). An ether-linked LPA (1-O-hexadecylglycerol 3-phosphate) has much decreased mitogenic activity as compared with the ester-linked analogue at concentrations less than 25 microM, and becomes cytotoxic at higher concentrations. Hexadecylphosphate, which lacks a glycerol backbone, has negligible activity. On a molar basis, diacyl phosphatidic acid (PA) is about equally potent as the corresponding LPA analogue, showing similar acyl-chain-length dependence; the data argue against the possibility that the mitogenic action of PA is due to contaminating traces of LPA. Although the short-chain analogues of LPA and PA fail to antagonize the action of long-chain (L)PAs, the polyanionic drug suramin inhibits LPA- and PA-induced, DNA synthesis in a reversible and dose-dependent manner, at concentrations [IC50 (concn. giving 50% inhibition) approximately 70 microM] that do not affect epidermal-growth-factor-induced DNA synthesis. Suramin appears to act in the early G0/G1 phase of the cell cycle, blocking immediate responses to LPA such as phosphoinositide hydrolysis. We conclude that both LPA and PA can function as growth-promoting phospholipids, with the fatty acid chain length being a major determinant of mitogenic potency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Line
  • DNA Replication / drug effects*
  • Endothelins / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Kinetics
  • Lysophospholipids / antagonists & inhibitors
  • Lysophospholipids / pharmacology*
  • Phosphatidic Acids / antagonists & inhibitors
  • Phosphatidic Acids / pharmacology*
  • Structure-Activity Relationship
  • Suramin / pharmacology*
  • Thymidine / metabolism


  • Endothelins
  • Lysophospholipids
  • Phosphatidic Acids
  • Suramin
  • Epidermal Growth Factor
  • Thymidine