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Journal of Biochemistry Advance Access originally published online on February 21, 2007
Journal of Biochemistry 2007 141(4):545-552; doi:10.1093/jb/mvm062
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© 2007 The Japanese Biochemical Society.

The Effect of V(III)–Adenine Complex on Yeast as a Model of Eukaryotic Cells

Jerzy Piatkowski1,*, Halina Podsiadly2 and Krystyna Bukietynska2

1Institute of Genetics and Microbiology Wroclaw University, 51-148 Wroclaw, Ul. Przybyszewskiego 63/77; and 2Krystyna Bukietyþska and Halina Podsialy, Faculty of Chemistry, Wroclaw University, 50-383 Wroclaw, Ul. Joliot-Curie 14

*To whom the correspondence should be addressed. Tel: +0048 071 375 62 17, Fax: +0048 071 325 21 51, E-mail: jurekp{at}microb.uni.wroc.pl

Received November 23, 2006; Accepted January 31, 2007


  Abstract

The dinuclear µ-okso vanadium (III) complex compound H4V2OCl4(Ad)2 synthesized in our laboratory was investigated as a potential cytotoxic agent against yeast cells. The results of these studies could be helpful in the explanation of the mechanism governing the V (III) compound action on yeast as a simple model of eukaryotic cells. The important factors influencing the toxicity of this complex compound are: the stage of the yeast life cycle, the rate of growth and the pH of reaction mixture. The lethal effect was distinctly stronger when the reaction mixture was slightly acidic (pH = 4). In such solutions V(III) mononuclear species with adenine was relatively stable, and during the time of experiment possibly only a slow oxidation process to V(IV) occurred. In the solutions with pH = 7, several hydrolytic, perhaps mixed—valence, polynuclear species were present and their action on the yeast cells was rather weak. The increased lethal activity of this compound in acidic solutions may be useful in specific treatment against cancer cells whose cytoplasm and/or closest surrounding has lower pH value. The next important result was an observation that the killing activity of this compound was enhanced for yeast cells being in log phase. Also these which had a slower rate of growth (possessing some auxotrophic mutations) were more resistant than those growing faster. The extent of yeast mutagenesis caused by the complex compound is negligible, as the number of mutants found in experiments was within the limit of experimental error. These results are promising and the investigated complex can be considered as a potential anti cancer agent.

Key Words: adenine, anti-cancer drugs, cancer treatment, vanadium complex compound, yeast

Abbreviations: V(III), trivalent vanadium; IR, infra red; c.f.u., colony forming units; VA, adenine-vanadium complex


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