Antioxidants: Friends or foe in prevention or treatment of cancer: The debate of the century

There are a number of intrinsic (e.g. oncogenes) and extrinsic (e.g. radiation and inflammation) factors, which may arise in reactive oxygen species (ROS), resulting in DNA instability and then cancer. In this situation, initial cancerous cells would balance the harmful effects of ROS by switching on the protective effects in a longstanding manner. In normal conditions, ROS have an important role in signal transduction and gene transcription, nevertheless, ROS may act as a trigger for carcinogenesis via persistent DNA injuries as well as mutations in p53 such as conditions observed in skin, hepatocellular, and colon cancers. Some compounds like paclitaxel are able to attack cancer cells through generation of ROS or interfering with ROS metabolism, while there are a few anti-angiogenesis compounds without toxicity such as endostatin, which act as anti-neoplastic only together with another chemotherapeutic drug. Furthermore, some anti-cancer agents like piperlongumine bind to the active sites of several key cellular antioxidants including glutathione S transferase and carbonyl reductase 1 only in the cancer cells. Although the natural antioxidants can alone or in combination with the diet provide some benefits for chemoprevention, their position in cancer therapy, especially initial stages of carcinogenesis is breaking down. On the other hand antioxidants can promote the survival of detached cells from extra cellular medium playing dual activities with respect to tumorigenesis through inhibition of tumorigenesis by preventing oxidative injuries to DNA and otherwise maintenance of tumor by promoting cell survival via metabolic rescue. Hopefully, more details of antioxidant and anti-neoplastic mechanisms become clear day by day, which have made researchers renew the strategy for designing cancer prevention or treatment (C) 2013 Elsevier Inc. All rights reserved.