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FASEB J

Title:		Loading-induced antitumor capability of murine and human urine
Author(s):		Wu D; Fan Y; Liu S; Woollam MD; Sun X; Murao E; Zha R; Prakash R; Park C; Siegel AP; Liu J; Agarwal M; Li BY; Yokota H;
Address:		"Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, China. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA. Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA. Integrative Nanosystems Development Institute, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA. Graduate School of Engineering, Mie University, Mie, Japan. Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA. Simon Cancer Research Center, Indiana University School of Medicine, Indianapolis, IN, USA. Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA"
Journal Title:		FASEB J
Year:		2020
Volume:		20200415
Issue:		6
Page Number:		7578 - 7592
DOI:		10.1096/fj.202000096R
ISSN/ISBN:		1530-6860 (Electronic) 0892-6638 (Print) 0892-6638 (Linking)
Abstract:		"While urine has been considered as a useful bio-fluid for health monitoring, its dynamic changes to physical activity are not well understood. We examined urine's possible antitumor capability in response to medium-level, loading-driven physical activity. Urine was collected from mice subjected to 5-minute skeletal loading and human individuals before and after 30-minute step aerobics. Six cancer cell lines (breast, prostate, and pancreas) and a mouse model of the mammary tumor were employed to evaluate the effect of urine. Compared to urine collected prior to loading, urine collected post-activity decreased the cellular viability, proliferation, migration, and invasion of tumor cells, as well as tumor weight in the mammary fat pad. Detection of urinary volatile organic compounds and ELISA assays showed that the loading-conditioned urine reduced cholesterol and elevated dopamine and melatonin. Immunohistochemical fluorescent images presented upregulation of the rate-limiting enzymes for the production of dopamine and melatonin in the brain. Molecular analysis revealed that the antitumor effect was linked to the reduction in molecular vinculin-linked molecular force as well as the downregulation of the Lrp5-CSF1-CD105 regulatory axis. Notably, the survival rate for the high expression levels of Lrp5, CSF1, and CD105 in tumor tissues was significantly lowered in the Cancer Genome Atlas database. Collectively, this study revealed that 5- or 10-minute loading-driven physical activity was sufficient to induce the striking antitumor effect by activating the neuronal signaling and repressing cholesterol synthesis. The result supported the dual role of loading-conditioned urine as a potential tumor suppressor and a source of diagnostic biomarkers"
Keywords:		"Adolescent Adult Animals Cell Line, Tumor Disease Models, Animal Dopamine/urine Exercise/physiology Female Humans Male Mammary Neoplasms, Animal/urine Melatonin/urine Mice Mice, Inbred C57BL PC-3 Cells Signal Transduction/physiology Urine/*physiology Youn;"
Notes:		"MedlineWu, Di Fan, Yao Liu, Shengzhi Woollam, Mark D Sun, Xun Murao, Eiji Zha, Rongrong Prakash, Rahul Park, Charles Siegel, Amanda P Liu, Jing Agarwal, Mangilal Li, Bai-Yan Yokota, Hiroki eng R01 AR052144/AR/NIAMS NIH HHS/ R03 CA238555/CA/NCI NIH HHS/ R01 AR52144/National Institute of Health/International Research Support, N.I.H., Extramural 2020/04/16 FASEB J. 2020 Jun; 34(6):7578-7592. doi: 10.1096/fj.202000096R. Epub 2020 Apr 15"