Dual role of hydrogen peroxide in cancer: possible relevance to cancer chemoprevention and therapy

Abstract

Accumulating evidence suggests that hydrogen peroxide (H(2)O(2)) plays an important role in cancer development. Experimental data have shown that cancer cells produce high amounts of H(2)O(2). An increase in the cellular levels of H(2)O(2) has been linked to several key alterations in cancer, including DNA alterations, cell proliferation, apoptosis resistance, metastasis, angiogenesis and hypoxia-inducible factor 1 (HIF-1) activation. It has also been observed that the malignant phenotype of cancer cells can be reversed just by decreasing the cellular levels of H(2)O(2). On the other hand, there is evidence that H(2)O(2) can induce apoptosis in cancer cells selectively and that the activity of several anticancer drugs commonly used in the clinic is mediated, at least in part, by H(2)O(2). The present report discusses that the high levels of H(2)O(2) commonly observed in cancer cells may be essential for cancer development; these high levels, however, seem almost incompatible with cell survival and may make cancer cells more susceptible to H(2)O(2)-induced cell death than normal cells. An understanding of this dual role of H(2)O(2) in cancer might be exploited for the development of cancer chemopreventive and therapeutic strategies.