Dietary Antioxidants and their Molecular Targets in Oxidative Stress Mediated Cancer Progression

Cancer is a complex disease and is currently the leading cause of mortality and morbidity across the globe. Dysregulated bioenergetics is one of the hallmarks of cancer cells and is characterized by increased activity of several enzymes of metabolic pathways. Consequently, cancer cells produce higher levels of reactive oxygen species (ROS) which contribute to their enhanced proliferation and survival over normal cells. Elevated levels of ROS cause oxidative stress, redox imbalance, DNA damage, activation of oncogenes, chronic inflammation and eventually cancer. Additionally, ROS mediated oxidative stress activates several oncogenic signaling cascades including PI3K/Akt pathway, NF-κB pathway, cyclooxygenase pathway, JAK/STAT pathway, angiogenesis and metastasis. To maintain redox balance and neutralize the detrimental effects of ROS, normal cells exhibit an antioxidant defence system, comprising of both enzymatic and non-enzymatic division. Activation of Nrf2 signaling pathway is the key regulatory pathway that helps in restoring the cellular redox homeostasis. Extensive research in the past decades has witnessed the potential health benefits of dietary antioxidants alone or in combination in the prevention of several chronic diseases, including cancer. A number of antioxidants from dietary backgrounds such as epigallocatechin gallate, resveratrol, curcumin, phloretin, berberine and lycopene have shown appreciable potential as a chemopreventive agent without causing significant toxicity. This chapter presents an extensive analysis of existing knowledge on the protective effects of various dietary antioxidants against cancer with a focus on oxidative stress, redox homeostasis and dysregulated cellular signaling leading to cancer cell proliferation, survival and metastasis.

Keywords: Antioxidants, Cancer, Oxidative stress, Reactive oxygen species, Redox homeostasis.