Distinct DNA Metabolism and Anti-proliferative Effects of Goat Urine Metabolites: An Explanation for Xeno-tumor Heterogeneity

Author(s): Ajay Kumar, Swati Swami, Nilesh K. Sharma*

Journal Name: Current Chemical Biology

Volume 14 , Issue 1 , 2020

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Abstract:

Background: The 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 ruminants like goat.

Methods: Fresh urine samples were collected from healthy ruminants (cow, goat, buffalo, ox), non-ruminant animals (horse, jenny) and human. Further, these urine samples were subjected to fractionation by drying, vortexing, centrifugation and sterile filtration in DMSO extraction solvent. Collected urine DMSO fraction (UDF) samples from all sources were subjected to DNA metabolizing assay with plasmid DNA pBR322 and genomic DNA of MCF-7 cells. Next, based on the discernible DNA metabolizing effects of goat UDF among other sources, goat UDF was tested for anti-proliferative effects upon HCT-116 and MCF-7 cells using Trypan blue dye exclusion assay.

Results: This paper reports that goat UDF possesses very clear DNA metabolizing effects (up to 95%) upon plasmid and genomic DNA compared to other ruminants, non-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 clear anti-proliferative effects upon HCT-116 (up to 75%) and MCF-7 (up to 40%).

Conclusion: This study signifies the clear differences in DNA metabolizing effects of goat UDF over other selected animal sources. Furthermore, the observed DNA metabolizing effects of goat UDF well correlate with anti-proliferative effects upon HCT-116 and MCF-7 cells. This study is a first report to show the comparison of urine metabolites among various animals. Interestingly, findings propose an indirect link that may support the possible reasons behind xeno-tumor heterogeneity in the form of rare occurrences of colorectal and mammary cancer in goat over other ruminants, non-ruminants and human.

Keywords: Microbiome, neoplasms, metabolites, ruminants, therapy, urine.

[1]
Chen J, Vitetta L. Inflammation-modulating effect of butyrate in the prevention of colon cancer by dietary fiber. Clin Colorectal Cancer 2018; 17(3): e541-4.
[http://dx.doi.org/10.1016/j.clcc.2018.05.001] [PMID: 29866614]
[2]
Nilendu P, Roychoudhary S, Deshpande K, Sharma NK. Therapeutic peptide mimetics looking for a turn to block aberrant players of malignancy. Curr Cancer Ther Rev 2017; 13: 1-18.
[http://dx.doi.org/10.2174/1573394713666170615115259]
[3]
Patel H. Pritish Nilendu, Devashree Jahagirdar, Jayanta K. Pal, Sharma NK. Modulating non-cellular components of microenvironmental heterogeneity: A masterstroke in tumor therapeutics. Cancer Biol Ther 2018; 19(1): 3-12.
[http://dx.doi.org/10.1080/15384047.2017.1394538] [PMID: 29219656]
[4]
India State-Level Disease Burden Initiative Cancer Collaborators. The burden of cancers and their variations across the states of India: the Global Burden of Disease Study 1990-2016 Lancet Oncol 2018 Sep; 11S1470-2045(18): 30447-9.
[5]
Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328(19): 1365-71.
[http://dx.doi.org/10.1056/NEJM199305133281901] [PMID: 8474513]
[6]
Nakanishi M, Chen Y, Qendro V, et al. Effects of walnut consumption on colon carcinogenesis and microbial community structure. Cancer Prev Res (Phila) 2016; 9(8): 692-703.
[http://dx.doi.org/10.1158/1940-6207.CAPR-16-0026] [PMID: 27215566]
[7]
Mehta RS, Nishihara R, Cao Y, et al. Association of dietary patterns with risk of colorectal cancer subtypes classified by fusobacterium nucleatum in tumor tissue. JAMA Oncol 2017; 3(7): 921-7.
[http://dx.doi.org/10.1001/jamaoncol.2016.6374] [PMID: 28125762]
[8]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[9]
Nilendu P, Sarode SC, Jahagirdar D, et al. Mutual concessions and compromises between stromal cells and cancer cells: driving tumor development and drug resistance. Cell Oncol (Dordr) 2018; 41(4): 353-67.
[http://dx.doi.org/10.1007/s13402-018-0388-2] [PMID: 30027403]
[10]
Gill S, Thomas RR, Goldberg RM. Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther 2003; 18(7): 683-92.
[http://dx.doi.org/10.1046/j.1365-2036.2003.01735.x] [PMID: 14510741]
[11]
Chino XMS, et al. Cooked chickpea consumption inhibits colon carcinogenesis in mice induced with azoxymethane and dextran sulfate sodium. J Am Coll Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet 2010; 375: 1030-47.
[12]
Stein A, Atanackovic D, Bokemeyer C. Current standards and new trends in the primary treatment of colorectal cancer. Eur J Cancer 2011; 47(Suppl. 3): S312-4.
[http://dx.doi.org/10.1016/S0959-8049(11)70183-6] [PMID: 21943995]
[13]
Löhr CV. One hundred two tumors in 100 goats (1987-2011). Vet Pathol 2013; 50(4): 668-75.
[http://dx.doi.org/10.1177/0300985812471544] [PMID: 23341420]
[14]
Mammary tumors in ruminants. Acta Agric Slov 2013; 102(2): 83-6.
[http://dx.doi.org/10.2478/acas-2013-0031]
[15]
Puthia M, Storm P, Nadeem A, Hsiung S, Svanborg C. Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells). Gut 2014; 63(1): 131-42.
[http://dx.doi.org/10.1136/gutjnl-2012-303715] [PMID: 23348960]
[16]
Guo Y, Wu R, Gaspar JM, et al. DNA methylome and transcriptome alterations and cancer prevention by curcumin in colitis-accelerated colon cancer in mice. Carcinogenesis 2018; 39(5): 669-80.
[http://dx.doi.org/10.1093/carcin/bgy043] [PMID: 29547900]
[17]
Waluga M, Zorniak M, Fichna J, Kukla M, Hartleb M. Pharmacological and dietary factors in prevention of colorectal cancer. J Physiol Pharmacol 2018; 69(3)
[PMID: 30149368]
[18]
Kumar A, Bhatkar D, Jahagirdar D, Sharma NK, Sharma NK. Non-homologous end joining inhibitor SCR-7 to exacerbate low dose doxorubicin cytotoxicity in HeLa. J Cancer Prev 2017; 22(1): 47-54.
[http://dx.doi.org/10.15430/JCP.2017.22.1.47] [PMID: 28382286]
[19]
Sharma NK, Ajay Kumar, Amresh Kumar Yadav. Method for genotoxic and apoptotic compositions of cow urine DMSO fraction towards breast carcinoma. Indian Patent Application No: 201821025084 (2018). Date of filing 05/07/2018 Filed/Published 2018.
[20]
Jahagirdar D, Purohit S, Sharma NK. Combinatorial use of DNA ligase inhibitor L189 and temozolomide potentiates cell growth arrest in HeLa. Curr Cancer Ther Rev 2018; 14: 1-7.
[21]
Sharma NK. Ajay Kumar “Method of using goat urine DMSO fraction as anti-proliferative and apoptotic cell death compounds against cancer cells and composition thereof” Date of filing 21/12/2018 (Ref No: 201821048505). Filed/Published 2018.


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Article Details

VOLUME: 14
ISSUE: 1
Year: 2020
Published on: 27 May, 2020
Page: [48 - 57]
Pages: 10
DOI: 10.2174/2212796814666200310102512
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