Colorectal Cancer and Mitochondrial Dysfunctions of the Adjunct Adipose Tissues: A Case Study

Abstract

Excess body weight has been causally linked to an increased risk of different cancer types, including colorectal cancer (CRC) but the mechanisms underlying this association are practically unknown. We investigate redox state-superoxide (SO) generation rate, activity of complex I in electron transport chain (ETC) of mitochondria and of dinitrosyl iron complexes by electron paramagnetic resonance; activity of matrix metalloproteinase (gelatinase) MMP-2 and MMP-9 by gel zymography of adipose tissues (AT) from 46 patients (64.0 ± 1.6 y.o.) with CRC (II–III stages, pT2–3N0–2M0) in the AT adjacent to tumor (ATAT) and at a distance of 3 cm from the tumor (ATD) to follow the connection of the AT redox state with some of the tumor microenvironment indicators. We have incubated the AT species with the tumor necrosis factor α (TNF-α) to follow its influence on the measured values. As a control, normal AT (NAT) obtained during the liposuction is used. Tumor-induced changes in mitochondrial ETC of ATAT, particularly for Complex I, lead to the enhanced SO generation and consequent oxidative modifications of DNA in ATAT (up to 6.1 times higher than that in NAT and 3.7 times higher than that in ATD, p < 0.05). Gelatinase activity in ATAT is significantly higher than in ATD. A considerable effect of TNF-α on ATAT and ATD (but not on NAT, i.e., only on the tissues where the reprogramming of metabolism has already occurred under the influence of tumor) manifested in increase of cellular hypoxia, gelatinase activity, and SO generation rate is observed. The results can be used for better understanding the mechanism(s) of metabolic symbiosis of tumor and AT as well as serving as a basis for new therapeutic approaches.

Redox changes in obesity, metabolic syndrome, and diabetes

“…More recently, research focus has shifted towards metabolic cross-talk as one of the integral aspects of cancer-adipose tissue two-way communication [ 214 , 215 ]. Several exciting studies, including our own, showed not only that metabolic support provided by adipocytes is instrumental for cancer progression and metastasis but that it is redox-sensitive [ [216] , [217] , [218] ] and obesity-mediated [ [219] , [220] , [221] ] ( Fig. 6 ).…”

Selectedin vitro methods to determine antioxidant activity of hydrophilic/lipophilic substances

“…Nowadays, methods allowing immediate monitoring of free radicals alone and in reaction with a complex system (for example cells and tissues) are very important and widely used (Burlaka et al, 2018;Bukhari et al, 2018;Borbat et al, 2001). These methods mainly include ESR and electromagnetic spin resonance, also called electron paramagnetic resonance spectroscopy, EPR.…”

Parenchyma sparing multicomponent liver resection strategy for multiple bilobar synchronous colorectal cancer metastasis

“…Liver resection remains the main strategy in case of primary malignancies and metastatic liver injury by colorectal cancer (CRC). The parenchyma sparing strategy in liver surgery has proven as an effective way of acute liver failure prevention, “small‐for‐size” liver syndrome, and oncological safety . Successful resection should be considered when the preserved part of the liver parenchyma has not only adequate blood inflow through the system of the hepatic artery and portal vein, but also effective drainage into the system of the inferior vena cava.…”

“…The parenchyma sparing strategy in liver surgery has proven as an effective way of acute liver failure prevention, "small-for-size" liver syndrome, and oncological safety. 1,2 Successful resection should be considered when the preserved part of the liver parenchyma has not only adequate blood inflow through the system of the hepatic artery and portal vein, but also effective drainage into the system of the inferior vena cava. That is why, avoiding venous congestion causing the dysfunction of regeneration processes and in the worst cases tissue necrosis considered a significant factor in liver interventions planning.…”