The Role of Oxidative Stress and Its Counteractive Utility in Colorectal Cancer (CRC)

SIMPLE SUMMARY: Colorectal cancer (CRC) is very common throughout the world. Despite an improved outcome with the current treatment regimen, a huge number of patients relapse and develop drug resistant disease. Excessive production of reactive oxygen/nitrogen species (ROS/RNS) results in the development of oxidative stress that is closely implicated in the development and progression of CRC. Additionally, the tumor cells can also show an adaptive response against persistent oxidative stress which may lead to chemoresistance. Interestingly, this increased oxidative stress could be manipulated to selectively eradicate the tumor cells. This review depicts how an elevated oxidative stress disrupts different cell signaling pathways and presents the redox modulating agents that showed promising efficacy against CRC derived cell lines. ABSTRACT: An altered redox status accompanied by an elevated generation of reactive oxygen/nitrogen species (ROS/RNS) has been implicated in a number of diseases including colorectal cancer (CRC). CRC, being one of the most common cancers worldwide, has been reported to be associated with multiple environmental and lifestyle factors (e.g., dietary habits, obesity, and physical inactivity) and harboring heightened oxidative stress that results in genomic instability. Although under normal condition ROS regulate many signal transduction pathways including cell proliferation and survival, overwhelming of the antioxidant capacity due to metabolic abnormalities and oncogenic signaling leads to a redox adaptation response that imparts drug resistance. Nevertheless, excessive reliance on elevated production of ROS makes the tumor cells increasingly vulnerable to further ROS insults, and the abolition of such drug resistance through redox perturbation could be instrumental to preferentially eliminate them. The goal of this review is to demonstrate the evidence that links redox stress to the development of CRC and assimilate the most up-to-date information that would facilitate future investigation on CRC-associated redox biology. Concomitantly, we argue that the exploitation of this distinct biochemical property of CRC cells might offer a fresh avenue to effectively eradicate these cells.