Effects of genistein on the mitochondrial function and the antioxidant response in human colon cancer cells

Abstract

[eng] Colorectal cancer is the third most common malignancy in the world. Reactive oxygen species (ROS) play a pivotal role in cancer initiation and progression, with metastatic cells being producers of high levels of ROS. An impairment in the balance of ROS production and elimination can easily lead to mitochondrial dysfunction, affecting cellular processes such as mitochondrial biogenesis, mitochondrial function and antioxidant response, as well as cell viability. Several antioxidant compounds have been tested on cancer cells, such as genistein, a phytoestrogen found in high amounts in soybeans. The objective of the present study was to determine the effect of treatment with genistein (100 µM) on mitochondrial biogenesis and function, and antioxidant response in human colorectal cancer cell lines in different stage. For this reason, cell viability, ROS production and expression of genes related to the processes of interest were analyzed. Specifically, the genes studied were: Sirt1, PGC1α, TFAM, mtSSB, NRF1, NRF2, ERRα, COX I and COX IV. The results suggest that genistein 100 μM modulates mitochondrial biogenesis in colorectal cell lines, and it produces different effects depending on the stage of tumor development that those cells are in, causing a beneficial effect in cells in early stages of cancer development, and a cytotoxic effect in metastatic cells. This could mean that the basal stress conditions in which cells from different stages are play a pivotal role in their response to treatment to genistein.