Membrane structure modulation, protein kinase C alpha activation, and anticancer activity of minerval

Mol Pharmacol. 2005 Feb;67(2):531-40. doi: 10.1124/mol.104.000778. Epub 2004 Nov 5.


Most drugs currently used for human therapy interact with proteins, altering their activity to modulate the pathological cell physiology. In contrast, 2-hydroxy-9-cis-octadecenoic acid (Minerval) was designed to modify the lipid organization of the membrane. Its structure was deduced following the guidelines of the mechanism of action previously proposed by us for certain antitumor drugs. The antiproliferative activity of Minerval supports the above-mentioned hypothesis. This molecule augments the propensity of membrane lipids to organize into nonlamellar (hexagonal H(II)) phases, promoting the subsequent recruitment of protein kinase C (PKC) to the cell membrane. The binding of the enzyme to membranes was marked and significantly elevated by Minerval in model (liposomes) and cell (A549) membranes and in heart membranes from animals treated with this drug. In addition, Minerval induced increased PKCalpha expression (mRNA and protein levels) in A549 cells. This drug also induced PKC activation, which led to a p53-independent increase in p21(CIP) expression, followed by a decrease in the cellular concentrations of cyclins A, B, and D3 and cdk2. These molecular changes impaired the cell cycle progression of A549 cells. At the cellular and physiological level, administration of Minerval inhibited the growth of cancer cells and exerted antitumor effects in animal models of cancer without apparent histological toxicity. The present results support the potential use of Minerval and related compounds in the treatment of tumor pathologies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cattle
  • Cell Line, Tumor
  • Cell Membrane / drug effects*
  • Cell Membrane / enzymology*
  • Cell Membrane / pathology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Growth Inhibitors / pharmacology
  • Humans
  • Liposomes
  • Oleic Acids / chemistry
  • Oleic Acids / pharmacology*
  • Protein Kinase C / metabolism*
  • Protein Kinase C-alpha
  • Stearic Acids / pharmacology*


  • 2-hydroxy-9-cis-octadecenoic acid
  • 5-octadecenoic acid
  • Antineoplastic Agents
  • Growth Inhibitors
  • Liposomes
  • Oleic Acids
  • Stearic Acids
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha