Quercetin ameliorates reactive oxygen species generation, inflammation, mucus depletion, goblet disintegration, and tumor multiplicity in colon cancer: Probable role of adenomatous polyposis coli, β‐catenin

Abstract

1,2 Dimethyl hydrazine (DMH), a cogent environmental toxicant, targets the colon. Previous reports suggest that DMH‐mediated dysregulation of the Wnt/β‐catenin pathway plays a vital role in the initial events of colon carcinogenesis. Our study was designed to investigate the effect of quercetin on DMH‐mediated colon cancer by targeting adenomatous polyposis coli (APC) and β‐catenin in Wistar rats. Animals were pretreated orally with quercetin at doses of either 25 or 50 mg/kg bodyweight (bw) and DMH at a dose of 20 mg/kg bw subcutaneously up to the 15th week and sacrificed after the 30th week. DMH administration leads to reactive oxygen species generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Increased inflammatory and proliferative proteins were observed in DMH‐induced colon cancerous rats. DMH treatment also led to dysregulation in the apoptotic pathway with decreased Bax:Bcl‐2 ratio. Quercetin pretreatment ameliorates DMH‐induced proliferation, activities of detoxifying enzymes, and putative early markers (mucin depletion and goblet cell disintegration) in colonic tissue. It also significantly regulates APC and β‐catenin expression and inhibits tumor incidence and multiplicity. Histological results further confirm the beneficial role of quercetin in averting DMH‐induced pathological alterations.

A Comprehensive View on the Quercetin Impact on Colorectal Cancer

“…Testing System Reference ↓ COX-2, iNOS, NF-κB In vivo: Wistar rats [134] ↓ SLC1A5 glutamine transporter…”

“…In the development of CRC, cellular growth and proliferation mechanisms need to be altered for the progression of the disease. It is noteworthy that quercetin is documented, in Table 3 , as an inhibitor of these processes both in vivo and in vitro [ 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ]; however, the molecular mechanisms are not fully understood due to its multitude of targets and, quite often, lack of analysis beyond the mere description of the phenomenon [ 136 , 137 , 138 , 139 , 140 , 141 ].…”

The molecular basis of the anticancer properties of quercetin

“…Similar results were recorded on HT-29 cells, where quercetin (50 µM) enhanced cisplatin-induced apoptosis. The effect was partially due to the inhibition of the activation of NF-κB expression (mucin depletion and goblet cell disintegration), adenomatous polyposis coli and β-catenin, and tumor incidence and multiplicity [102]. Similar results were recorded on N-methyl nitrosoureainduced rat colon cancer, where quercetin (50 mg/kg) blocked the overexpression of Wnt5a and up-regulated the expression of Axin-1, and decreased the serum level of TAG72 and GAL3 in colon cancer bearing rats [103].…”

From Diospyros kaki L. (Persimmon) Phytochemical Profile and Health Impact to New Product Perspectives and Waste Valorization

“…Due to the association of reactive oxygen species with cancer and cardiovascular diseases, antioxidants have been considered a promising route for the prevention and treatment of these diseases, especially considering the links observed between diets rich in fruits and vegetables, and reducing the risks of developing cancer [ 96 ]. The phenolic compound quercetin, for instance, has been described as being able to effectively recycle vitamin E and has also been registered as being able to decrease cell damage caused by oxidation, inflammation, and tumorigenesis [ 97 , 98 , 99 , 100 , 101 , 102 ].…”