Nucleic acid synthesis in cancerous cells under the effect of gnidilatimonoein from Daphne mucronata

Life Sci. 2004 Feb 27;74(15):1869-76. doi: 10.1016/j.lfs.2003.08.039.

Abstract

Cytotoxicity evaluation of gnidilatimonoein, the most active isolated diterpene ester from Daphne mucronata [Sadeghi H, Mianabadi M, Yazdanparast R, (2002) Journal of Tropical. Medicinal Plant1 3: 169-173], revealed the strong antiproliferative activity among several different human cancer cell lines (K562, CCRF-CEM, HL-60 and MOLT-4 leukemia cell lines, LNCaP-FGC-10 a prostate cancer cell line) and a mouse BALB/C fibrosarcoma cell line (WEHI-164). Using flow cytometry technique, it was found that treatment of the most responsive cells (K562) with gnidilatimonoein inhibited the progression of cells through G1 phase by almost 15% compared to the untreated cells. The population of the treated cells in the S and G2 phases also reduced by 8.3% and 5.4%, respectively. Based on the extent of [3H]-thymidine and [3H]-uridine incorporation into DNA and RNA, respectively, the major metabolic effects of gnidilatimonoein were found to be mainly on DNA and to a less extent on RNA synthesis. Additionally, the activity of inosine-5'-monophosphate dehydrogenase (IMPDH), under the effects of genidilatimonoein, was reduced in the treated cells by 44%. These data strongly suggest that the purine biosynthetic pathway is significantly affected by gnidilatimonoein.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / drug effects*
  • Cell Line, Tumor / ultrastructure
  • DNA / biosynthesis*
  • Daphne*
  • Diterpenes / pharmacology*
  • Electrophoresis, Agar Gel
  • Flow Cytometry
  • IMP Dehydrogenase / drug effects
  • IMP Dehydrogenase / metabolism
  • Microscopy, Electron
  • Nucleic Acid Synthesis Inhibitors / pharmacology*
  • Plant Preparations / pharmacology

Substances

  • Diterpenes
  • Nucleic Acid Synthesis Inhibitors
  • Plant Preparations
  • gnidilatimonoein
  • DNA
  • IMP Dehydrogenase