Peroxiredoxin III : a candidate for drug resistance to chemotherapy : a thesis presented in partial fulfillment of the requirements for the degree of Master of Science in Biochemistry at Massey University, Palmerston North, New Zealand

Abstract

The development of drug resistance to chemotherapeutic drugs is a serious obstacle in the successful treatment of cancer. New cancer drugs are continually being developed with the goal of increasing the effectiveness of chemotherapy. However, new mechanisms of drug resistance are also continually being identified. Understanding the mechanisms of drug resistance is a vital step in identifying new drug targets which may prevent or reduce the development of drug resistance. A recent unpublished study identified peroxiredoxin III (prx III) as being up-regulated in breast cancer cells in culture following exposure to the commonly used anti-cancer drug doxorubicin. Doxorubicin and the almost identical drug epirubicin have multiple mechanisms of activity. One function of these drugs is to increase intracellular hydrogen peroxide (H 2 O 2 ) concentrations to induce cell death. As prx III is a mitochondrial protein which reduces H 2 O 2 , it has been suggested that increased expression of prx III may contribute to the development of drug resistance to doxorubicin or epirubicin. However, before such a role for prx III in the development of drug resistance can be further investigated, prx III expression needs to be examined in patients undergoing chemotherapy. The aim of this study was to examine prx III expression in the white blood cells of patients undergoing chemotherapy with epirubicin, and in healthy control subjects. Additionally, as the activity of a number of peroxiredoxins has been shown to be modulated through the formation of complexes and over-oxidation, complex formation and over-oxidation in response to treatment with doxorubicin or epirubicin was also examined. The results of this study could identify a new target for preventing or reducing the development of drug resistance. While the sample sizes were too small to draw conclusions, some patients showed a change in the expression of peroxiredoxin III following chemotherapy with epirubicin, suggesting that further investigation into the expression of peroxiredoxin III following chemotherapy would be worthwhile.