Nucleic acid synthesis in cancerous cells under the effect of gnidilatimonoein from Daphne mucronata.
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.
Yazdanparast
Razieh
R
Institute of Biochemistry and Biophysics, University of Tehran, P. O. Box 13145-1384, Tehran, Iran. yazdan@ibb.ut.ac.ir
Sadeghi
Heibatollah
H
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000648:ultrastructure; D004247:DNA / Q000096:biosynthesis*; D032364:Daphne; D004224:Diterpenes / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D007168:IMP Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology
D004224:Diterpenes; D019384:Nucleic Acid Synthesis Inhibitors; D028321:Plant Preparations; C482573:gnidilatimonoein; D004247:DNA; D007168:IMP Dehydrogenase