Oxidative Stress and Cellular Senescence: The Key Tumor-promoting Factors in Colon Cancer and Beneficial Effects of Polyphenols in Colon Cancer Prevention

Background: Colon cancer is the third leading cause of cancer-related deaths worldwide. Colon tumorigenesis is a sequential process called “Adenoma-carcinoma sequence”. The alimentary habits, obesity, heavy alcohol consumption, inflammatory bowel diseases, family history of colon cancer, oxidative stress, and cellular senescence are the major risk factor influencing colon cancer development. Senescence contributes to the aging process as well as the development and progression of colon cancer. However, the precise mechanism underlying the aging-related progress of colon cancer is yet to be answered. Recent studies proposed that the senescent cell secretes Senescence-Associated Secretory Phenotype (SASP) includes pro-inflammatory cytokines, interleukins, growth factors, and proteases actively involved in the creation of pro-tumorigenic microenvironment. Objective: This review aims to provide an overview of ROS influence cellular senescence and colon cancer development as well as summarize the antioxidant and antiaging activity of natural flavonoids. Many of the studies had reported that pro-aging genes suppress cancer and various ‘markers’ are used to identify senescent cells in vitro and in vivo. The SASP of the cells may act as a link between senescence and cancer. Conclusion: This review facilitates a better understanding and might contribute to diagnostic and prognostic systems as well as to find out the novel and targeted therapeutic approaches. Additionally, we focused on the potential role of natural flavonoids in colon cancer therapies and highlighting the flavonoid-based treatments as innovative immunomodulatory strategies to inhibit the growth of colon cancer.