The role of reactive oxygen species in tumor cells apoptosis induced by landomycin A

L. V. Lehka, R. R. Panchuk, W. Berger, Ju Rohr, R. S. Stoika

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Landomycin A (LA) is a new antitumor antibiotic of angucycline group, possessing high antitumor activity against cancer cells of different origin, which induces early apoptosis in target cells. It was shown that under LA action the level of reactive oxygen species (ROS) in human T-leukemia cells had increased 5.6 times in comparison to control already at the 1st hour after the addition of studied antibiotic to the culture medium. At the 6th hour after incubation of cells with LA the nucleosomal DNA cleavage, chromatin condensation and nucleus fragmentation were observed, indicating apoptotic cell death. Catalase (scavenger of hydrogen peroxide), mannitol (scavenger of hydroxyl radicals) and superoxide dismutase (scavenger of superoxide radicals) reduced the level of ROS production under LA, suggesting the generation of H2O2, OH and O2- radicals, respectively. It was revealed that catalase and mannitol effectively inhibited LA-mediated tumor cell death, increasing 2.5 times the percentage of alive cells in comparison to LA. However, superoxide dismutase had no significant inhibitory effect on cytotoxic activity of LA, indicating the minor role of superoxide anions in the implementation of antitumor activity of this antibiotic. Combination of catalase, mannitol and superoxide dismutase with LA increased 4-fold the percentage of alive cells in comparison to the action of LA. Dynamics of ROS formation confirms that the increase of ROS is a very rapid process, but at the same time it is not a direct consequence of apoptosis triggering, mediated by mitochondria.

Original languageEnglish
Pages (from-to)72-82
Number of pages11
JournalUkrainian Biochemical Journal
Volume87
Issue number5
DOIs
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015, Natsional’na Akademiya Nauk Ukrainy. All rights reserved.

Keywords

  • Apoptosis
  • Landomycins
  • Malignant cells
  • Reactive oxygen species (ROS)

ASJC Scopus subject areas

  • Biochemistry

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