Christina Higdon

Introduction. Colorectal cancer is the 3^rd most common cancer and is a leading cause of death among cancers. ¹ The cancer initiates in colon epithelial cells, which multiply and accumulate mutations, leading to tumorigenesis and possible metastasis. Cancer cells with high rates of replication often lead to creation of reactive oxidative species (ROS), which causes inflammation, instability, damage, and further proliferaton.^2,3 The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is identified as the major antioxidant response regulator against ROS and proteins created by upregulation of Nrf2 relieve oxidative damage to the cell.⁴ This pathway is activated by dietary phytochemicals, such as isothiocyanates. Sulforaphane (SFN), an isothiocyanate derivative found in Brassica vegetables, has been studied for its Nrf2 pathway promotion and relation to cancer.^5-8 Studies suggest sulforaphane may be a promising cancer preventing agent, though others suggest it may further cancer promotion.⁹ Methods. Researchers utilized human colorectal cells, mice, and human clinical trials to understand SFN’s effects. Colon cells were grown with SFN and selenium, with added ROS to understand combinatory effects on levels of thioredoxin reductase using flow cytometric analysis.¹⁰ Researchers investigated human consumption of SFN and its precursor in beverages, related levels of toxin excretion, and bioavailability of SFN using cyclocondensation and mass spectrometry.¹¹ Additional studies analyzed SFN relation to histone deacetylase expression and novel NmrA-like redox sensor 2 psuedogene (NMRAL2P), using PCR and immunoprecipitation.^12,13 Cancer promoting effects of SFN were analyzed in a study that compared protein activities in colon cells to cancer lines Caco-2 and HT-29 using PCR and immunocytochemistry.¹⁴ Results. Colon cells treated with SFN and selenium combined best reduced thioredoxin reductase levels, providing ROS protection.¹⁰ SFN beverage consumption found increases in excretion of toxins and better bioavailability in SFN rich beverages than SFN-precursor rich.¹¹ SFN suppressed tumor growth and decreased histone deacetylase activity at certain administration schedules.¹² NMRAL2P was upregulated in cells treated with SFN through the Nrf2 pathway and coregulated an antioxidant protein.¹³ Colon cancer cell lines treated with SFN induced different protein expression that could conflict with cancer treatment and suggest cancer cells may be protected by SFN.¹⁴ Conclusions. Studies indicate SFN plays an important role in ROS control via Nrf2. SFN offers promising effects on prevention, however, upregulation may contribute to progression. Further research and clinical studies need to be done to ensure efficacy in all stages of cancer, dosage, bioavailability, and safety before used as a form of prevention.

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