Reactive oxygen species in cancer

Abstract

Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumor development and progression. However, tumor cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signaling to effectively deprive cells from ROS-induced tumor promoting events, towards tipping the balance to ROS-induced apoptotic signaling. Alternatively, therapeutic antioxidants may prevent early events in tumor development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signaling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumor cells, their detoxification, their cellular effects, as well as the major signaling cascades they utilize, but also provides an outlook on their modulation in therapeutics.

TMEFF2 shedding is regulated by oxidative stress and mediated by ADAMs and transmembrane serine proteases implicated in prostate cancer

“…ROS levels also regulate several signalling pathways in cancer (Hanahan and Weinberg, 2000; Liou and Storz, 2010), including PCa (Khandrika et al, 2009), which led us to hypothesise that ROS levels regulate TMEFF2 shedding. To investigate this hypothesis, we pre‐treated AP‐TMEFF2 HEK293 cells with the ROS scavenger NAC or the NADPH oxidase inhibitor APOC prior to stimulation with PMA, a known inducer of ROS generation (Datta et al, 2000) and ADAM17 activator (Brill et al, 2009).…”

The mitochondrial dynamics in cancer and immune-surveillance

“…Although a detailed analysis of ROS effects on tumor growth is beyond the scope of this review (see [112] for details), we would like to stress that ROS accumulation could represent a priming signal during the tumor onset, this being the probable cause of mtDNA mutations often found in cancer cells [112,113]. Elevated ROS can also promote upregulation of several oncogenic signalling pathways, such as Ras/MAPK/ERK, PI3K/Akt and IKK/KF-B, and can favour tumor cell proliferation, apoptosis-resistance and cell migration (see [112] for a review).…”

PKCι counteracts oxidative stress by regulating Hsc70 in an esophageal cancer cell line

“…Oxidative stress plays dual roles in cancer cell survival during tumorigenesis, as sublethal oxidative stress can activate oncogenic signals but severe oxidative stress can cause cell death or senescence (Liou and Storz 2010;Brown and Bicknell 2001). To survive and expand under exogenous or intrinsic oxidative stress, cancer cells co-opt several cellular regulatory pathways controlling oxidative adaptation to maintain cell survival.…”