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2014 | 70 | 05 |

Tytuł artykułu

Effect of hypoxia on toxicity induced by anticancer agents in cardiomyocyte culture

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
The main goal of the study was to determine whether hypoxia augments the toxicity of anticancer drugs towards cardiomyocytes. Drugs selected for this experiment were those that disturb the cardiac redox equilibrium. Cardiomyocytes were incubated for 24 h with doxorubicin, tirapazamine, and 5-fluorouracil, each at three doses, under normoxia and under 50% and 90% hypoxia. The cytotoxic effect was evaluated on the basis of the percentage of living cells, cell vitality (assessed by the MTT assay), and morphology. In addition, the oxidative marker and pH value were determined. Varied protective effects of hypoxia on cell morphology were observed in all cases except the medium concentration of tirapazamine. The 50% hypoxia prevented the toxic effects of all tested drugs. The 90% hypoxia, on the other hand, was effective against the cytotoxic action of doxorubicin and 5-fluoruracil, but the cytotoxicity of tirapazamine increased. It was found that under the 90% hypoxia the oxidative stress observed under normoxia and the 50% hypoxia was greatly reduced. The study revealed that the above drugs did not activate anaerobic glycolysis.

Wydawca

-

Rocznik

Tom

70

Numer

05

Opis fizyczny

p.287-291,fig.,ref.

Twórcy

autor
  • Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland
autor
  • Medical Biology Unit, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland
autor
  • Medical Biology Unit, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland
  • Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland
  • Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland
autor
  • Medical Biology Unit, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland
  • Department of Animal Anatomy and Histology, University of Life Sciences in Lublin, Akademicka 12, 20-950, Lublin, Poland
autor
  • Medical Biology Unit, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland

Bibliografia

  • 1. Ashley N., Poulton J.: Mitochondrial DNA is a direct target of anti-cancer anthracycline drugs. Biochem. Biophys. Res. Commun. 2009, 378, 450-455.
  • 2. Donovan L., Welford S. M., Haaga J., LaManna J., Strohl K. P.: Hypoxia – implications for pharmaceutical developments. Sleep and Breathing 2010, 14, 291-298.
  • 3. Dorie M. J., Brown J. M.: Modification of the antitumor activity of chemotherapeutic drugs by the hypoxic cytotoxic agent tirapazamine. Cancer Chemother Pharmacol. 1997, 39, 361-366.
  • 4. Dudka J., Burdan F., Korga A., Iwan M., Madej-Czerwonka B., Cendrowska-Pinkosz M., Korobowicz-Markiewicz A., Jodlowska-Jedrych B., Matysiak W.: Intensification of doxorubicin-related oxidative stress in the heart by hypothyroidism is not related to the expression of cytochrome P450 NADPH-reductase and inducible nitric oxide synthase, as well as activity of xanthine oxidase. Oxid Med Cell Longev., doi: 10.1155/2012/139327, 2012.
  • 5. Elwell J. H., Siim B. G., Evans J. W., Brown J. M.: Adaptation of Human Tumor Cells to Tirapazamine under Aerobic Conditions. Biochem Pharmacol. 1997, 54, 249-257.
  • 6. Feola, Garrone O., Occelli M.: Cardiotoxicity after anthracycline chemotherapy in breast carcinoma: effects on left ventricular ejection fraction, troponin I and brain natriuretic peptide. Intern. J. Cardiol. 2011, 148, 194-198.
  • 7. Fulbright J. M.: Review of cardiotoxicity in pediatric cancer patients: during and after therapy. Cardiol. Res. Pract. doi: 10.4061/2011/942090, 2011.
  • 8. Lebrecht D., Walker U. A.: Role of mtDNA lesions in anthracycline cardiotoxicity. Cardiovasc Toxicol. 2007, 7, 108-113.
  • 9. Minotti G., Menna P., Salvatorelli E., Cairo G., Gianni L.: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004, 56, 185-229.
  • 10. Reddy S. B., Williamson S. K.: Tirapazamine: a novel agent targeting hypoxic tumor cells. Expert Opin Investig Drugs. 2009, 18, 77-87.
  • 11. Siim B. G., Pruijn F. B., Sturman J. R., Hogg A., Hay M. P., Brown J. M., Wilson W. R.: Selective potentiation of the hypoxic cytotoxicity of tirapazamine by its 1-N-oxide metabolite SR 4317. Cancer Res. 2004, 64, 736-742.
  • 12. Sliwinska J., Dudka J., Korga A., Burdan F., Matysiak W., Jodlowska-Jedrych B., Mandziuk S., Dawidek-Pietryka K.: Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca²⁺ balance protein levels. Oxid Med Cell Longev. 2012, doi:10.1155/2012/890826.
  • 13. Wouters B. G., Delahoussaye Y. M., Evans J. W., Birrell G. W., Dorie M. J., Wang J., MacDermed D., Chiu R. K., Brown J. M.: Mitochondrial dysfunction after aerobic exposure to the hypoxic cytotoxin tirapazamine. Cancer Res. 2001, 61, 145-152.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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