Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1968 Mar 1;36(3):485–496. doi: 10.1083/jcb.36.3.485

STUDIES ON THE MECHANISM OF ACTION OF PEDERINE

Agnese Brega 1, Arturo Falaschi 1, Luigi De Carli 1, Mario Pavan 1
PMCID: PMC2107367  PMID: 5650903

Abstract

Pederine, a drug extracted from the coleopter Paederus fuscipes, inhibits the growth of in vitro cultured cell lines at concentrations of the order of 1.5 nanogram/ml. Cytological examination shows a generalized cytotoxic effect. Analysis of macromolecular syntheses by the use of radioactive precursors shows that pederine causes an almost immediate block of protein and DNA synthesis, without affecting RNA synthesis. The effects on the synthesis of the two types of macromolecules remain nearly simultaneous even at the lowest active concentrations of pederine. Studies with cell-free systems show that the drug inhibits protein synthesis, whereas it is ineffective on the DNA-polymerizing activity. It seems, therefore, that the drug acts primarily on the amino acid-polymerizing system, and that the effect on DNA is secondary. This idea is strengthened by the observation that puromycin, a specific inhibitor of protein synthesis, also affects promptly DNA synthesis of in vitro cultured cells. Other authors have shown the same phenomenon with a number of inhibitors of protein synthesis; the properties of pederine support, therefore, the view that continuous protein synthesis is necessary for the maintenance of DNA replication in higher organisms.

Full Text

The Full Text of this article is available as a PDF (637.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARONSON A. I., SPIEGELMAN S. On the nature of the ribonucleic acid synthesized in the presence of chloramphenicol. Biochim Biophys Acta. 1961 Oct 14;53:84–95. doi: 10.1016/0006-3002(61)90796-x. [DOI] [PubMed] [Google Scholar]
  2. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cairns J. Autoradiography of HeLa cell DNA. J Mol Biol. 1966 Jan;15(1):372–373. doi: 10.1016/s0022-2836(66)80233-4. [DOI] [PubMed] [Google Scholar]
  4. DECARLI L., MAIO J. J., NUZZO F., BENERECETTI A. S. CYTOGENETIC STUDIES WITH ALKALINE PHOSPHATASE IN HUMAN HETEROPLOID CELLS. Cold Spring Harb Symp Quant Biol. 1964;29:223–231. doi: 10.1101/sqb.1964.029.01.026. [DOI] [PubMed] [Google Scholar]
  5. EAGLE H. Nutrition needs of mammalian cells in tissue culture. Science. 1955 Sep 16;122(3168):501–514. doi: 10.1126/science.122.3168.501. [DOI] [PubMed] [Google Scholar]
  6. EAGLE H. Propagation in a fluid medium of a human epidermoid carcinoma, strain KB. Proc Soc Exp Biol Med. 1955 Jul;89(3):362–364. doi: 10.3181/00379727-89-21811. [DOI] [PubMed] [Google Scholar]
  7. FJELDE A. Human tumor cells in tissue culture. Cancer. 1955 Jul-Aug;8(4):845–851. doi: 10.1002/1097-0142(1955)8:4<845::aid-cncr2820080434>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  8. GOLD M., HELLEINER C. W. DEOXYRIBONUCLEIC ACID POLYMERASE IN L CELLS. I. PROPERTIES OF THE ENZYME AND ITS ACTIVITY IN SYNCHRONIZED CELL CULTURES. Biochim Biophys Acta. 1964 Feb 17;80:193–203. [PubMed] [Google Scholar]
  9. Littlefield J. W., Jacobs P. S. The relation between DNA and protein synthesis in mouse fibroblasts. Biochim Biophys Acta. 1965 Dec 9;108(4):652–658. doi: 10.1016/0005-2787(65)90061-4. [DOI] [PubMed] [Google Scholar]
  10. MAALOE O., HANAWALT P. C. Thymine deficiency and the normal DNA replication cycle. I. J Mol Biol. 1961 Apr;3:144–155. doi: 10.1016/s0022-2836(61)80041-7. [DOI] [PubMed] [Google Scholar]
  11. NATHANS D. INHIBITION OF PROTEIN SYNTHESIS BY PUROMYCIN. Fed Proc. 1964 Sep-Oct;23:984–989. [PubMed] [Google Scholar]
  12. Plaut W., Nash D., Fanning T. Ordered replication of DNA in polytene chromosomes of Drosophila melanogaster. J Mol Biol. 1966 Mar;16(1):85–93. doi: 10.1016/s0022-2836(66)80264-4. [DOI] [PubMed] [Google Scholar]
  13. STOKER M., MACPHERSON I. SYRIAN HAMSTER FIBROBLAST CELL LINE BHK21 AND ITS DERIVATIVES. Nature. 1964 Sep 26;203:1355–1357. doi: 10.1038/2031355a0. [DOI] [PubMed] [Google Scholar]
  14. SZYBALSKI W., IYER V. N. CROSSLINKING OF DNA BY ENZYMATICALLY OR CHEMICALLY ACTIVATED MITOMYCINS AND PORFIROMYCINS, BIFUNCTIONALLY "ALKYLATING" ANTIBIOTICS. Fed Proc. 1964 Sep-Oct;23:946–957. [PubMed] [Google Scholar]
  15. Soldati M., Fioretti A., Ghione M. Cytotoxicity of pederin and some of its derivatives on cultured mammalian cells. Experientia. 1966 Mar 15;22(3):176–178. doi: 10.1007/BF01897720. [DOI] [PubMed] [Google Scholar]
  16. TERNI M., LO MONACO G. B. Coltura continua di cellule derivate da embrione umano. Sperimentale. 1958 May-Jun;108(3):177–185. [PubMed] [Google Scholar]
  17. Taylor E. W. Control of DNA synthesis in mammalian cells in culture. Exp Cell Res. 1965 Nov;40(2):316–332. doi: 10.1016/0014-4827(65)90265-x. [DOI] [PubMed] [Google Scholar]
  18. Young C. W. Inhibitory effects of acetoxycycloheximide, puromycin, and pactamycin upon synthesis of protein and DNA in asynchronous populations of HeLa cells. Mol Pharmacol. 1966 Jan;2(1):50–55. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES