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Inhibition of Macromolecular Biosynthesis in Cultured L1210 Mouse Leukemia Cells by Thalicarpine (NSC 68075)

National Cancer Institute-Veterans Administration Medical Oncology Branch, Veterans Administration Hospital, Washington, D. C. 20422

The plant alkaloid thalicarpine inhibits the synthesis of DNA, RNA, and protein in cultured L1210 cells. Significant inhibition of thymidine incorporation into L1210 DNA and uridine into RNA by 100 µM thalicarpine occurs within 20 min. Whereas inhibition of DNA synthesis is only partially reversible, that of RNA is nearly reversed when the cells are washed free of the drug. Thalicarpine also inhibits early steps of nucleotide triphosphate biosynthesis.

DNA from L1210 cells inhibited by thalicarpine sediments along with the bulk DNA from uninhibited cells whereas the RNA from inhibited cells is deficient in all species of RNA and in particular, rapidly labeled, heterogenously sedimenting RNA. Inhibition of protein synthesis by thalicarpine probably occurs at some early phase of its biosynthetic scheme. Thalicarpine is notable for its multiple and diverse modes of action, all or part of which may be responsible for its chemotherapeutic effect.

Received 5/18/73. Accepted 8/24/73.