Induction of cell cycle arrest by the carbazole alkaloid Clauszoline-I from Clausena vestita D. D. Tao via inhibition of the PKCδ phosphorylation

Eur J Med Chem. 2012 Jan;47(1):214-20. doi: 10.1016/j.ejmech.2011.10.047. Epub 2011 Nov 4.

Abstract

Sixteen carbazole alkaloids from Clausena vestita D. D. Tao were extracted, and their anti-tumor activities were evaluated. Among the extracts, Clauszoline-I exhibited an obvious growth inhibitory activity against several cancer cell lines through its ability to induce cell cycle arrest in the S and G2/M phases. A dramatic morphologic change with decreased F-actin staining and RhoA activity was found in Clauszoline-I treated HepG2 cells, in which the phosphorylation of PKCδ (Ser643) was inhibited. Our results indicated that induction cell cycle arrest by Clauszoline-I might be achieved by decreasing the RhoA activity via the inhibition of PKCδ phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / pharmacology*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Proliferation / drug effects
  • Clausena / chemistry*
  • Hep G2 Cells
  • Humans
  • Phosphorylation / drug effects
  • Protein Kinase C-delta / chemistry
  • Protein Kinase C-delta / metabolism*
  • Serine / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Carbazoles
  • clauszoline-I
  • Serine
  • Protein Kinase C-delta
  • rhoA GTP-Binding Protein