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

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

Research output: Contribution to journalArticle

219 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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Camptothecin
Cell Cycle
Lymphocytes
Alkaloids
Experimental Leukemias
Plasmacytoma
DNA
Phytohemagglutinins
Mitosis
Mast Cells
Pharmaceutical Preparations
Non-Hodgkin's Lymphoma
Survivors
Neoplasms
Leukemia
Cell Proliferation
RNA
Cell Line
Survival
Proteins

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

Cite this

Studies on the antitumor activity, mechanism of action, and cell cycle effects of camptothecin. / Gallo, R C; Whang-Peng, J; Adamson, R H.

In: Journal of the National Cancer Institute, Vol. 46, No. 4, 04.1971, p. 789-95.

Research output: Contribution to journalArticle

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N2 - 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.

AB - 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.

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KW - Animals

KW - Antineoplastic Agents

KW - Autoradiography

KW - Carbon Isotopes

KW - Cell Transformation, Neoplastic

KW - DNA

KW - Lectins

KW - Leukemia, Experimental

KW - Lymphocytes

KW - Lymphoma, Large B-Cell, Diffuse

KW - Mast-Cell Sarcoma

KW - Mice

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KW - Neoplasm Proteins

KW - Neoplastic Cells, Circulating

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KW - Thymidine

KW - Tritium

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