Figure 32

Scheme showing the differential metabolism of PUFAs in normal and tumor cells. Normal cells exposed to anti-cancer drugs and radiation produce increased amounts of ROS. In response to this, normal cells produce enhanced amounts of lipoxins, resolvins and protectins from PUFAs that are released by the activation of phospholipase A₂. Infiltrating or local leukocytes and macrophages produce enhanced amounts of IL-6 and TNF-α that, in turn, enhance ROS generation and cause inflammation. If cell stores of PUFAs are adequate, activation of phospholipase A₂ (the type of phospholipase activated in normal and tumor cells may be distinctly different) leads to release of PUFAs to be converted to lipoxins, resolvins and protectins, which suppress leukocyte and macrophage activation, ROS generation and inflammation to protect normal cells from apoptosis. In the case of tumor cells, infiltrating leukocytes and macrophages produce enhanced amounts of IL-6 and TNF-α that produce excess amounts of ROS leading to inflammation. ROS damage DNA and aid in the progression of cancer. Tumor cells have decreased amounts of PUFAs that get are converted to pro-inflammatory eicosanoids due to activation of COX-2 and LO and thus, inflammation and cancer growth are perpetuated. Normal cells supplemented with PUFAs produce adequate amounts of lipoxins, resolvins and protectins that protect them from ROS, suppress inflammation and prevent actions of mutagens and carcinogens. On the other hand, tumor cells supplemented with PUFAs generate more free radicals, show enhanced lipid peroxidation that lead to apoptosis. Thus, normal cells exposed to PUFAs produce cytoprotective lipoxins, resolvins and protectins while tumor cells generate toxic hydroperoxy fatty acids.