Paraoxonases, oxidative stress, and breast cancer

Breast cancer (BC) is the main cause of cancer-related death among women worldwide. Oxidative stress is a disturbance of balance between oxidant and antioxidants in favor of oxidants. Paraoxonase (PON) enzymes (PON1, PON2, and PON3) are calcium-dependent hydrolases that are involved in the antioxidation process and are the products of three genes: PON1, PON2, and PON3. The association of PON1 with BC was based on a number of PON1 polymorphisms leading to low serum PON1 activity. This low PON1 activity contributes to an increase in oxidative stress and may promote BC development. In addition, PON2 and PON3 show antiapoptotic activity and antioxidative effects by reducing the formation of reactive oxygen species (ROS). Thus, higher concentrations in healthy breast cells are beneficial for cellular homeostasis. However, their antiapoptotic function, by decreasing ROS in cancerous breast cells, makes treatment of BC more difficult. There is limited information about the regulation of PONs and associated-molecular mechanisms between ROS and PONs in BC. Therefore, it is essential to evaluate the present data concerning the relationship between PONs and ROS and possible PON-dependent molecular mechanisms of cancer induction, especially for BC.