Genistein could play a crucial role in modulating three closely linked physiological processes altered during cancer: oxidative stress, mitochondrial biogenesis, and inflammation. However, genistein’s role in colorectal cancer remains unclear. We aimed to determine genistein’s effects in two colon cancer cells: HT29 and SW620, primary and metastatic cancer cells, respectively. After genistein treatment for 48 h, cell viability and hydrogen peroxide (H₂O₂) production were studied. The cell cycle was studied by flow cytometry, mRNA and protein levels were analyzed by RT-qPCR and Western blot, respectively, and finally, cytoskeleton remodeling and NF-κB translocation were determined by confocal microscopy. Genistein 100 µM decreased cell viability and produced G₂/M arrest, increased H₂O₂, and produced filopodia in SW620 cells. In HT29 cells, genistein produced an increase of cell death, H₂O₂ production, and in the number of stress fibers. In HT29 cells, mitochondrial biogenesis was increased, however, in SW620 cells, it was decreased. Finally, the expression of inflammation-related genes increased in both cell lines, being greater in SW620 cells, where NF-κB translocation to the nucleus was higher. These results indicate that high concentrations of genistein could increase oxidative stress and inflammation in colon cancer cells and, ultimately, decrease cell viability.

Breast cancer is the most common malignancy in women of developed countries. The aim of this study was to investigate the effects of the phytoestrogen genistein on the inflammatory profile in three breast cancer cell lines with different oestrogen receptors alpha (ERα) and beta (ERβ) ratio. MCF-7 (high ERα/ERβ ratio), T47D (low ERα/ERβ ratio), and MDA-MB-231 (ERα-negative) cells were treated with 1 µM of genistein for 48 h (cell proliferation and ROS production) or 4 h (mRNA expression of 18S, ERα, ERβ, pS2, Sirtuin1, IL-1β, NF-κB, COX-2, TGFβ1, PPARγ). Genistein caused a significant decrease in cell viability and an increase in ROS production in MCF-7, and the opposite happens in T47D cells. In addition, genistein rise pro-inflammatory and reduced anti-inflammatory genes expression in MCF-7, provoking the opposite effects in T47D cells. In conclusion, the phytoestrogen genistein could modulate the expression of inflammatory-related genes through its interaction with both ERs, and its effects depends on the ERα/ERβ ratio.

Selenium is a micronutrient which is found in many foods, with redox status modulation activity. Our aim was to evaluate the effects of two chemical forms of selenoamino acids, Seleno-L-methionine and Seleno-L-cystine (a diselenide derived from selenocysteine), at different concentrations on cell viability, hydrogen peroxide production, antioxidant enzymes, UCP2 protein expression, as well as lipid and protein oxidative damage in MCF-7 breast cancer cells. Results showed that Seleno-L-methionine did not cause an increase in hydrogen peroxide production at relatively low concentrations, accompanied by a rise in the antioxidant enzymes catalase and MnSOD, and UCP2 protein expression levels. Furthermore, a decrease in protein and lipid oxidative damage was observed at 10 µM concentration. Otherwise, Seleno-L-cystine increased hydrogen peroxide production from relatively low concentrations (100 nM) to a large increase at high concentrations. Moreover, at 10 µM, Seleno-L-cystine decreased UCP2 and MnSOD protein expression. In conclusion, the chemical form of selenoamino acid and their incorporation to selenoproteins could affect the regulation of the breast cancer cell redox status. Taken together, the results obtained in this study imply that it is important to control the type of selenium-enriched nutrient consumption, taking into consideration their composition and concentration.

Xanthohumol (XN) is a prenylated flavonoid known for its antioxidant and anti-inflammatory effects and has been studied as an anti-cancer agent. In this study, we aimed at analysing the effect of XN on a primary colorectal adenocarcinoma cell line, HT29, on cell viability, inflammatory and antioxidant gene expression, and metabolism. For this purpose, cells were treated with 10 nM and 10 µM XN, and cell viability, H₂O₂ production, lipid peroxidation and gene expression of inflammatory, antioxidant, and mitochondrial-related genes, as well as protein levels of metabolic enzymes, were determined. Results showed no significant effects on cell viability and a general decrease in pro-inflammatory, antioxidant and mitochondrial biogenesis gene expression with the lower concentration of XN. Furthermore, glucose and oxidative metabolism enzymes were also reduced. These results suggest that XN treatment, at low doses, could stop the proliferation and progression of HT29 cells by downregulating inflammatory signals and cell metabolism.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year survival rate of patients, and different efforts are being put into developing enhanced CRC screening programs. Currently, the faecal immunochemical test with a follow-up colonoscopy is being implemented for CRC screening. However, there is still a medical need to describe biomarkers that help with CRC detection and monitor CRC patients. The use of omics techniques holds promise to detect new biomarkers for CRC. In this review, we discuss the use of omics in different types of samples, including breath, urine, stool, blood, bowel lavage fluid, or tumour tissue, and highlight some of the biomarkers that have been recently described with omics data. Finally, we also review the use of extracellular vesicles as an improved and promising instrument for biomarker detection.

Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.