Drug resistance has been a critical problem in colon cancer therapy in the last years. While cancer therapies have been developed to counteract the proliferation of cancer cells, many agents also show cytotoxic side effects. Several treatments depend on cisplatin derivatives, fluoroacil, epirubicin, capecitabine, leucovorin or a combination of these agents, which yield critical benefits but in many cases also promote oxidative stress. The imbalance of the redox response induces various cellular effects but can also promote dysfunctional mitochondrial activity or mitochondrial damage, such as impairment of the respiratory chain and the loss of mitochondrial membrane potential with subsequent disruption of cellular bioenergetics. Therefore, metabolism changes in cancer that lead to increased reactive oxygen species (ROS) accumulation can be a way to promote a pivotal circuit that favor an increasing on ROS production. Consequently ROS induces chemoresistance mechanism that could be considered on basis of the effect: altered drug target sensitive, poor intracellular activation of pro-drugs or higher inactivation of active drugs; increase DNA repair, reduce apoptosis, alteration in drug stability, metabolism and distribution at the tumor zone, changes in the molecular targets that impairs the action of the drug by increasing the activity of the target route to be inhibited, stimulation of alternative routes, and ROS accumulation may be involved in these mechanisms. These cellular events have been related to therapies-oxidative stress induce. The use of antioxidants in combination with chemotherapeutic agents have shown promise to reduce the cytotoxicity of the agents. In this review, we discuss several agents currently used in colon cancer chemotherapy that induce ROS accumulation and new therapies used to counteract oxidative stress or its indirect effects.
|Translated title of the contribution||El estres oxidativo induce la resistencia a drogas en celulas de cancer de colon: nuevos mecanismos|
|Journal||Oxidative Medicine and Cellular Longevity|
|State||Unpublished - Apr 21 2018|