Role of Heme Iron in the Progression of Colon Cancer with APC Gene Mutated and Alternative Strategy for Colon Cancer Prevention
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Abstract
In 2020, colorectal cancer was the third-most prevalent cancer and the second-leading cause of cancer-related deaths worldwide. The adenomatous polyposis coli (APC) gene mutation promotes cancer progression by disrupting Wnt signaling. Heme iron, the fundamental component of red meat, can trigger oxidative stress and chronic inflammation, provoking Wnt signaling and resulting in excessive cell growth. Nevertheless, the cytotoxic effect of heme iron is rendered ineffective toward APC-mutated cells, increasing the risk of cell hyperproliferation. APC-mutated cells possess more efficient biotransformation of lipid peroxidation products and highly express nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in augmented antioxidant enzymes. While nuclear Nrf2 levels are raised in APC-mutated cells, the expression of heme oxygenase-1 is reduced compared to wild-type cells, thereby causing an increase in the proinflammatory process. In addition, APC-mutated cells escape apoptosis by impairing the nuclear factor kappa B inflammatory pathway. Heme iron further enhances chronic gut inflammation by causing an imbalance in the intestinal microbiota, thereby increasing cell growth. To minimize the risk of colon cancer, especially for those with an APC gene mutation, limiting the consumption of foods rich in heme iron such as red meat is advisable. Additionally, considering dietary supplements that provide antioxidant, anti-inflammatory, and gut microbiota modulation benefits could also be beneficial.
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