Mitochondrial oxidative stress drives tumor progression and metastasis: should we use antioxidants as a key component of cancer treatment and prevention?

Abstract

The functional role of oxidative stress in cancer pathogenesis has long been a hotly debated topic. A study published this month in BMC Cancer by Goh et al., directly addresses this issue by using a molecular genetic approach, via an established mouse animal model of human breast cancer. More specifically, alleviation of mitochondrial oxidative stress, via transgenic over-expression of catalase (an anti-oxidant enzyme) targeted to mitochondria, was sufficient to lower tumor grade (from high-to-low) and to dramatically reduce metastatic tumor burden by >12-fold. Here, we discuss these new findings and place them in the context of several other recent studies showing that oxidative stress directly contributes to tumor progression and metastasis. These results have important clinical and translational significance, as most current chemo-therapeutic agents and radiation therapy increase oxidative stress, and, therefore, could help drive tumor recurrence and metastasis. Similarly, chemo- and radiation-therapy both increase the risk for developing a secondary malignancy, such as leukemia and/or lymphoma. To effectively reduce mitochondrial oxidative stress, medical oncologists should now re-consider the use of powerful anti-oxidants as a key component of patient therapy and cancer prevention. Please see related research article: http://www.biomedcentral.com/1471-2407/11/191.

Figure 1

Tumor evolution is fueled by mitochondrial oxidative stress. The experiments by Goh et al. directly show that blocking mitochondrial ROS inhibits metastasis, indicating that mitochondrial oxidative stress promotes tumor progression and metastasis. The observed effects most likely involve the effects of ROS on both cancer cells and their surrounding tumor stroma. Cellular processes activated by ROS include DNA damage, autophagy/mitophagy, and aerobic glycolysis. Complementary studies have shown that ROS-induced activation of autophagy and aerobic glycolysis in cancer associated fibroblasts provide recycled nutrients (pyruvate, lactate, ketones, and glutamine, among others) for anabolic cancer cell growth, and protects these cancer cells against apoptosis. Importantly, anti-oxidants will prevent the oxidative stress, reducing tumor progression and metastasis. NAC, N-acetyl-cysteine; SOD2, mitochondrial superoxide dismutase; M-catalase, mitochondrially targeted catalase.