Potentiation of dna-reactive antineoplastic agents and protection against s-phase-specific agents by anguidine in chinese hamster ovary cells

Robert A Hromas, Barthel Barlogie, Douglas Swartzendruber, Benjamin Drewinko

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Anguidine, a protein synthesis inhibitor, has been shown to induce a reversible cell cycle arrest in exponentially growing Chinese hamster ovary cells. The effect of pretreatment with anguidine on the cytotoxicity of subsequently administered various chemotherapeutic agents, hyperthermia, and radiation was investigated. We found that anguidine greatly potentiated the cytotoxic activity of cis-dichlorodiammineplatinum(II) and melphalan by abolishing the initial shoulder and steeperilng the subsequent exponential portion of the survival curves. Bleomycin-induced cell kill was also potentiated by anguidine pretreatment but to a lesser extent. However, anguidine pretreatment did not substantially alter radiation cytotoxicity. In contrast, anguidine markedly reduced the lethal effect of hydroxyurea, 5-fluorouracil, and hyperthermia, three modalities with S-phase activity. To investigate whether both anguidine-induced potentiation and protection of cells by different antitumor agents were due to its induction of complete suspension of cycle traverse, experiments were also conducted with plateau-phase cultures. Whereas anguidine potentiated cis-dichlorodiammineplatinum(II) cytotoxicity in an identical fashion as noted in exponentially growing cells, its protective effect against lethal damage from Adriamycin was absent. Thus, it appears that the two opposite effects of anguidine modification of cell kill by cytotoxic agents (protection and potentiation) come about by two different mechanisms, with cell cycle arrest underlying cytoprotection and the mechanism of synergistic toxicity remaining obscure.

Original languageEnglish (US)
Pages (from-to)3070-3073
Number of pages4
JournalCancer Research
Volume43
Issue number7
StatePublished - Jul 1 1983
Externally publishedYes

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diacetoxyscirpenol
Cricetulus
Antineoplastic Agents
Ovary
Cytoprotection
Cell Cycle Checkpoints
Cisplatin
Fever
Radiation
Protein Synthesis Inhibitors
Melphalan
Hydroxyurea
Bleomycin
Cytotoxins
S Phase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Potentiation of dna-reactive antineoplastic agents and protection against s-phase-specific agents by anguidine in chinese hamster ovary cells. / Hromas, Robert A; Barlogie, Barthel; Swartzendruber, Douglas; Drewinko, Benjamin.

In: Cancer Research, Vol. 43, No. 7, 01.07.1983, p. 3070-3073.

Research output: Contribution to journalArticle

Hromas, Robert A ; Barlogie, Barthel ; Swartzendruber, Douglas ; Drewinko, Benjamin. / Potentiation of dna-reactive antineoplastic agents and protection against s-phase-specific agents by anguidine in chinese hamster ovary cells. In: Cancer Research. 1983 ; Vol. 43, No. 7. pp. 3070-3073.
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