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Br J Cancer. Jun 1999; 80(7): 971–980.
PMCID: PMC2363046
Mode of action of thiocoraline, a natural marine compound with anti-tumour activity
E Erba,1 D Bergamaschi,1 S Ronzoni,1 M Faretta,1 S Taverna,1 M Bonfanti,1 C V Catapano,2 G Faircloth,3 J Jimeno,4 and M D'Incalci1
1Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche ‘Mario Negri’, via Eritrea 62, Milano, 20157, Italy
2Department of Experimental Oncology, Hollings Cancer Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC, 29425-2850, USA
3PharmaMar USA Inc., 320 Putnam Avenue, Cambridge, MA, 02139-4616, USA
4Research and Development, PharmaMar S.A., Calle de la Calera 3, Tres Cantos, Madrid, 28760, Spain
Received July 7, 1998; Revised November 19, 1998; Accepted November 27, 1998.
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 α at concentrations that inhibited cell cycle progression and clonogenicity. These studies indicate that the new anticancer drug thiocoraline probably acts by inhibiting DNA polymerase α activity. © 1999 Cancer Research Campaign
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