Distinct DNA metabolism and anti-proliferative effects of goat urine metabolites: An explanation for xeno-tumor heterogeneity

BackgroundThe tumor microenvironment, including microbiome populations in the local niche of several types of solid tumors like mammary and colorectal cancer are distinct. The occurrence of one type of cancer over another varies from animals to human individuals. Further, clinical data suggest that specific cancer types such as mammary and colorectal cancer are rare in ruminant like goat.\n\nMethodsFresh urine samples were collected from healthy ruminates including cow, goat, buffalo, ox, horse, jenny and human and subjected to fractionation using drying, vortexing, centrifugation and sterile filtration in DMSO solvent. Collected urine DMSO fraction (UDF) samples from all sources were subjected DNA metabolizing assay with plasmid DNA pBR322 and genomic DNA of MCF-7 cells. Further, based on the discernible DNA metabolizing effects, goat UDF was tested for anti-proliferative effects upon HCT-116 and MCF-7 cells using Trypan blue due exclusion assay.\n\nResultsThis paper reports that goat UDF possesses very clear DNA metabolizing effects (up to 95%) upon plasmid and genomic DNA compared to other ruminants and human UDF samples. Interestingly autoclaving of goat UDF and other sample results in the significant loss of DNA metabolizing effects. In this way, data potentially indicate that the goat UDF sample contains metabolite or similar organic compounds. Further, in vitro treatment of the goat UDF sample shows discernible anti-proliferative effects upon HCT-116 (up to 75%) and MCF-7 (up to 40%).\n\nConclusionThis study signifies the clear differences in DNA metabolizing effects of goat UDF and well correlated with anti-proliferative effects upon HCT-116 and MCF-7 cells. This study is of first report to show the comparison of urine metabolites and an indirect link to support the possible reasons behind xeno-tumor heterogeneity as rare occurrences of colorectal and mammary cancer in goat over other ruminants and human.