Study of antioxidant response and mitochondrial function on I, II, III and IV stages in biopsies of colon cancer

Abstract

[eng] Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females. Oxidative stress and mitochondrial functionality play a very important role in carcinogenesis, progression and invasion. Oxidative stress allows cells to be more malignant during early stages and during metastasis but at the same time, too high levels of ROS can induce apoptosis. So, control of ROS amount by antioxidant enzymes is very important. During hypoxia a bad mitochondrial functionality increase ROS production and induces a Warburg effect on cells too. For all these reasons our main aim was to determine protein levels related to mitochondrial functionality such as complex IV of electron transport chain, ATP synthase and LDH; and related to antioxidant defence such as MnSOD, CuZnSOD and Catalase in biopsies of all stages of colorectal cancer both of tumoral and peritumoral tissues. Results showed that in stage II there is a downregulation of Complex IV and ATP synthase related to stage I, and in stage IV tended to be an increase of these complexes, indicating a mitochondrial functionality recovery. In contrast, LDH levels increased in stage II and decreased in stage III and IV of colorectal cancer indicating Warburg effect in stage II and reverse Warburg effect in later stages. Finally, all antioxidant enzymes increased in stage II and were downregulated in stage III and IV. Therefore, it could be concluded that there is an increase of hypoxia levels between stage I and II, which could increase ROS production, and consequently, an increase of antioxidant and LDH levels occurs. In contrast, in spite there could be higher hypoxia in stages III and IV, mitochondrial functionality increases to be more invasive, process known as Reverse Warburg effect, so LDH levels also decrease. Antioxidant enzymes were downregulated maybe to allow cells to increase ROS and to be more malignant.