Characterization of azoxymethane-induced colon tumor metastasis to lung in a mouse model relevant to human sporadic colorectal cancer and evaluation of grape seed extract efficacy

Abstract

The second leading cause of cancer-related deaths (both genders combined) in the United States is colorectal cancer (CRC). This emphasizes the need to develop both effective therapies for CRC patients and pre-clinical models mimicking human disease that carry translational potential in drug-development. Notably, at present there are no in situ models of CRC metastasis to lung. In our azoxymethane-induced colon tumorigenesis study in A/J mice assessing grape seed extract (GSE) efficacy, during necropsy we also found multiple lung nodules suggestive of colon tumor metastasis to lung that were significantly inhibited in GSE fed group. Both histopathological and molecular studies were performed to characterize and establish the origin of these lesions in lung. Histologically these nodules were determined as adenocarcinoma of mucin origin. Molecular analyses by immunohistochemistry (IHC) and RT-PCR revealed strong protein and transcript levels of colon specific markers CDX2 and CK20 in these lung nodules compared to uninvolved control lung tissue. Vis-à-vis, these nodules also showed minimally expressed lung specific biomarkers, specifically surfactant D and TTF-1, in IHC analysis. Additionally, 0.25% GSE supplementation in diet (w/w) decreased the incidence of these lung nodules by 53% and their total number by 66%. Together, the characterization of this unique in situ mouse model of CRC metastasis to lung provides translational opportunities in developing effective therapies to clinically manage and treat CRC at the advanced stage. Moreover, GSE efficacy in inhibiting CRC metastasis to lung in this model further supports its translational potential in controlling CRC growth, progression and metastasis in patients.

Evaluation of the Biological Efficiency of Silver Nanoparticles Biosynthesized Using Croton tiglium L. Seeds Extract against Azoxymethane Induced Colon Cancer in Rats

“…In addition, cytokeratin 20 was expressed severely in colonic tissues of AOM induced colon cancer. This was in accordance with Derry et al, (2014) who showed that cytokeratin 20 is considered as an additional colon biomarker and expressed virtually in epithelial cells in all cases of colorectal carcinomas. The present study revealed that C. tiglium nano-extract minimized severity of the inflammatory responses that is considered as criteria of malignancy and stage of colon cancer in nano-extract simult-treated group while these inflammatory responses were prevented completely in the post-treated group.…”

Animal Models of Colorectal Cancer: From Spontaneous to Genetically Engineered Models and Their Applications

“…AOM induces rodent colon carcinogenesis when administered over 6–8 weeks via subcutaneous or intraperitoneal injection, with a latency period ranging from 20 to 30 weeks [ 13 ]. The distribution of tumors developed in the small intestine and colon (predominantly in the distal colon) is similar to that observed in the human colon [ 21 , 40 ]. Histological and histochemical properties of AOM-induced tumors are similar to those described in humans, being classified as adenomas and adenocarcinomas.…”

Improving Soluble Phenolic Profile and Antioxidant Activity of Grape Pomace Seeds through Fungal Solid-State Fermentation

“…Due to the abundance of bioactive compounds in grape pomace seeds, particularly phenolic compounds, which comprise 5% to 8% of their weight, there has been widespread interest in exploring their potential applications [1]. These phenolics, including phenolic acids, flavonoids, and proanthocyanidins, possess various health-promoting properties such as antioxidant, antiinflammatory, and anticancer activities [2][3][4][5][6][7]. However, like many other plant matrices, grape pomace seeds contain a significant proportion of phenolic compounds existing in Foods 2024, 13, 1158 2 of 13 an insoluble form, especially after the maceration process of winemaking [8], which limits their further application based on the active phenolic compounds.…”