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Mode of action of thiocoraline, a natural marine compound with anti-tumour activity.

Abstract
Thiocoraline, a new anticancer agent derived from the marine actinomycete Micromonospora marina, was found to induce profound perturbations of the cell cycle. On both LoVo and SW620 human colon cancer cell lines, thiocoraline caused an arrest in G1 phase of the cell cycle and a decrease in the rate of S phase progression towards G2/M phases, as assessed by using bromodeoxyuridine/DNA biparametric flow cytometric analysis. Thiocoraline does not inhibit DNA-topoisomerase II enzymes in vitro, nor does it induce DNA breakage in cells exposed to effective drug concentrations. The cell cycle effects observed after exposure to thiocoraline appear related to the inhibition of DNA replication. By using a primer extension assay it was found that thiocoraline inhibited DNA elongation by DNA polymerase alpha at concentrations that inhibited cell cycle progression and clonogenicity. These studies indicate that the new anticancer drug thiocoraline probably acts by inhibiting DNA polymerase alpha activity.
AuthorsE Erba, D Bergamaschi, S Ronzoni, M Faretta, S Taverna, M Bonfanti, C V Catapano, G Faircloth, J Jimeno, M D'Incalci
JournalBritish journal of cancer (Br J Cancer) Vol. 80 Issue 7 Pg. 971-80 (Jun 1999) ISSN: 0007-0920 [Print] England
PMID10362104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • Depsipeptides
  • Peptides
  • thiocoraline
  • DNA
  • DNA-Directed DNA Polymerase
  • Bromodeoxyuridine
Topics
  • Anti-Bacterial Agents (pharmacology)
  • Antibiotics, Antineoplastic (pharmacology)
  • Bromodeoxyuridine (metabolism)
  • Cell Cycle (drug effects)
  • Cell Division (drug effects)
  • DNA (drug effects, metabolism)
  • DNA-Directed DNA Polymerase (drug effects)
  • Depsipeptides
  • Flow Cytometry
  • Humans
  • Inhibitory Concentration 50
  • Peptides
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

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