Influence of mitoxantrone on nucleic acid synthesis on the T‐47D breast tumor cell line

Ahmad R. Safa, Nasser Chegini, Michael T. Tseng

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Mitoxantrone exerts growth inhibitory effects, suppresses [3H]‐thymidine as well as [3H]‐uridine incorporation, and induces ultrastructural alterations in T‐47D human breast tumor cells. At low concentration (10−9M) the drug induced little effect on cell proliferation; cell growth kinetics were inhibited at a concentration of 10−5M. [3H]‐thymidine and [3 H]‐uridine incorporation declined rapidly at the concentrations tested (10−9, 10−7, and 10−5 M), revealing a potent effect on metabolic activity of the cultured cells. The sharpest decline in DNA and RNA synthesis occurred within the first 2 hr of drug treatment. Serial ultrastructural examinations indicated definitive alterations in chromatin structure, disintegration of nucleolar components as early as 2 hr after drug treatment, and complete segregation of nucleolar components following 8‐hr exposure to concentrations of the drug between 10−5 and 10−7 M. A distinct increase in the density of mito‐chrondrial matrix was evident. The in vitro data presented in this report demonstrate the growth inhibitory and antimetabolic effects of mitoxantrone on human breast tumor cells and suggest that the drug may be a promising antitumor agent.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalJournal of Cellular Biochemistry
Volume22
Issue number2
DOIs
StatePublished - 1983
Externally publishedYes

Keywords

  • breast tumor cell line
  • mitoxantrone
  • nucleic acid synthesis
  • thymidine
  • uridine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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