New approach to mechanism of action of paclitaxel by means of BioArena studies

Erno Tyihák, Ágnes M. Móricz, Péter G. Ott, Michal L. Hajnos, Kazimierz Głowniak

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The accumulation of hydrogen peroxide (H2O2) is an early and crucial step in paclitaxel-induced cancer cell death before commitment of the cells to apoptosis. In these intracellular events formaldehyde (HCHO) as endogenous, indispensable component may be present mainly as hydroxymethyl groups and so there is a possibility of its endogenous interaction with H 2O2 in which singlet oxygen (1O2) and excited HCHO (H*CHO) can be formed. 1O2 can interact with H2O molecules and in this interaction dihydrogen trioxide (H2O3) is formed. The disproportion of this molecule - among others - results in ozone (O3). It is supposed that this reaction series is also valid for the conditions in layer chromatographic spots after inoculation. Results with paclitaxel support this idea. Using BioArena as a complex bioautographic system the HCHO molecules could be captured with well-known endogenous HCHO capture molecules (l-arginine, glutathione) in the spots of paclitaxel on the TLC/OPLC adsorbent layer after inoculation. Capture of HCHO resulted in a dose-dependent decrease of the antibacterial activity of paclitaxel. The antibacterial activity of paclitaxel in the chromatographic spots can be increased dramatically by using Cu(II) ions as HCHO-mobilizing and carrier ions in the culture medium. The HCHO molecule can N-hydroxymethylate the C3' amide of paclitaxel. By applying an O3 scavenger (e.g. indigo carmine) this oxidant, as a key reaction product of HCHO, could be detected indirectly in chromatographic spots of paclitaxel. It seems that these small molecules - from HCHO to endogenous O3 - may be crucial factors of the mechanism of antiproliferative action of the paclitaxel including killing of bystander cancer cells also. It seems that the basic molecule (paclitaxel) does not have a direct effect on the bacterial cells; its induction of the formation of H2O2 molecules (and indirectly HCHO molecules) may, however, be resulting in this complicated process.

Original languageEnglish
Pages (from-to)331-336
Number of pages6
JournalJournal of Planar Chromatography - Modern TLC
Volume21
Issue number5
DOIs
Publication statusPublished - Oct 1 2008

Keywords

  • BioArena
  • Bioautography
  • Formaldehyde cycle
  • Hydrogen peroxide
  • OPLC
  • Ozone
  • TLC

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry

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