Studies on the antitumor activity, mechanism of action, and cell cycle effects of camptothecin

R C Gallo, J Whang-Peng, R H Adamson

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222 Citations (Scopus)

Abstract

Camptothecin was active in increasing survival time in mice bearing various experimental leukemias. In addition, it produced 70–90% long-term survivors in mice bearing leukemias L5178Y or K1964. It was also active against the plasma cell tumor YPC-1 but less effective against a mast cell tumor and a reticulum cell sarcoma. The alkaloid was also cytotoxic in vitro against three cell lines. Studies using human lymphocytes stimulated by phytohemagglutinin (PHA) indicated that DNA synthesis was strongly inhibited with concentrations of the drug that did not affect RNA or protein synthesis. Camptothecin not only inhibited DNA synthesis but also caused a G2 “lesion” which prevented subsequent mitosis. It did not have cytocidal effects on resting “G0” lymphocytes. However, when “G0” lymphocytes exposed to the alkaloid were subsequently stimulated to enter cycle, their division was still blocked. These observations not only imply that eventual cell proliferation is necessary for the antitumor activity of camptothecin, but also suggest that the drug may be useful for tumors with long G1 intervals.
Original languageEnglish
Pages (from-to)789-95
Number of pages7
JournalJournal of the National Cancer Institute
Volume46
Issue number4
Publication statusPublished - Apr 1971
Externally publishedYes

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Keywords

  • Alkaloids
  • Animals
  • Antineoplastic Agents
  • Autoradiography
  • Carbon Isotopes
  • Cell Transformation, Neoplastic
  • DNA
  • Lectins
  • Leukemia, Experimental
  • Lymphocytes
  • Lymphoma, Large B-Cell, Diffuse
  • Mast-Cell Sarcoma
  • Mice
  • Mitosis
  • Neoplasm Proteins
  • Neoplastic Cells, Circulating
  • RNA
  • Thymidine
  • Tritium
  • Journal Article

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