A comparison of the action of amifostine and melatonin on DNA-damaging effects and apoptosis induced by idarubicin in normal and cancer cells

Ireneusz Majsterek, Ewa Gloc, Janusz Blasiak, Russel J. Reiter

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Amifostine is a well-known cell protector and its actions involve free radical scavenging, which is also considered as a mechanism underlying the protective actions of melatonin, a secretory product of the pineal gland. In this work we compared the action of 14 mM amifostine and 50 μM melatonin on DNA damage and apoptosis induced by idarubicin in normal human lymphocytes, leukemic K562 cells and HeLa cancer cells. We employed the alkaline comet assay and pulse-field gel electrophoresis to estimate DNA damage. Apoptosis was evaluated by caspase 3 activity assay assisted by the comet assay to evaluate DNA fragmentation and DAPI staining for detection of morphological changes in chromatin. We found that idarubicin induced apoptosis in normal and cancer cells and its level was correlated with the extent of DNA strand breaks. Amifostine reduced apoptosis and DNA damage in normal cells, but it potentiated these effects in cancer cells in this in vitro study. Melatonin protected both normal and cancer cells against genotoxic treatment and apoptosis induced by idarubicin. We conclude that despite its recognized potential as an antioxidant, melatonin should be considered with caution when used in combination with cancer chemotherapy agents, especially in the case of leukemias.

Original languageEnglish (US)
Pages (from-to)254-263
Number of pages10
JournalJournal of pineal research
Volume38
Issue number4
DOIs
StatePublished - May 1 2005

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Keywords

  • Amifostine
  • Apoptosis
  • DNA damage
  • Idarubicin
  • Melatonin

ASJC Scopus subject areas

  • Endocrinology

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