Transient/chronic microenvironmental
hypoxia that exists within a majority of solid
tumors has been suggested to have a profound influence on
tumor growth and therapeutic outcome. Since the functions of novel
antioxidant proteins,
peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use
thioredoxin (Trx) as an electron donor and Trx is a substrate for
thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following
hypoxia. Here we show a dynamic change of
glutathione homeostasis in
lung cancer A549 cells and an up-regulation of Prx I and Trx following
hypoxia. Western blot analysis of 10 human
lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx
proteins in
lung cancer tissues. Immunohistochemical analysis of the
lung cancer tissues confirmed an augmented Prx I and Trx expression in
cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in
lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in
lung cancer cells may well represent an attempt of
cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.