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Background-The purpose of our study was to show the distinction between the apoptotic and anti-proliferative signaling of phytosterols and cholesterol enrichment in prostate cancer cell lines, mediated by the differential transcription of caveolin-1, and N-myc downstream regulated gene1 (NDRG1), a pro-apoptotic androgen-regulated tumor suppressor.Methods-PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 72 h, followed by trypan blue dye exclusion measurement of necrosis and cell growth measured with a Coulter counter. Sterol induction of cell growth-suppressor gene expression was evaluated by mRNA transcription using RT-PCR, while cell cycle analysis was performed by FACS analysis. Altered expression of Ndrg1 protein was confirmed by Western blot analysis. Apoptosis was evaluated by real time RT-PCR amplification of P53, Bcl-2 gene and its related pro-and antiapoptotic family members.Corresponding Author: Godwin O. Ifere Ph.D, Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley DR. S.W. Atlanta, GA. 30314, Telephone: 404-880-6977, Fax: 404-880-8065, gifere@cau.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

Background Alginate‐encapsulated islet xenografts have restored normoglycemia in diabetic animals for various periods of time. Plausible mechanisms of graft failure in vivo include immune rejection and hypoxia. We sought to understand the effects of encapsulated adult porcine islet (API) dosage on the peritoneal dissolved oxygen (DO) level in correlation to the achieved glycemic regulation in diabetic mice. Methods Adult porcine islets encapsulated in barium alginate were transplanted intraperitoneally in streptozotocin diabetic BALB/c mice at 6000 and 4000 islet equivalents (IEQ) and in normal mice at 500 IEQ; APIs encapsulated in calcium alginate were transplanted at 6000 IEQ in diabetic mice. In all cases, cell‐free barium alginate capsules containing a perfluorocarbon emulsion were co‐implanted for DO measurements using 19F NMR spectroscopy. Blood glucose levels and peritoneal DO were measured over 60 days or until graft failure. Explanted capsules were evaluated microscopically and histologically. Results Both barium and calcium alginate‐encapsulated APIs at 6000 IEQ reversed diabetes until day 60; barium alginate‐encapsulated APIs at 4000 IEQ also reversed diabetes but with a higher failure rate. Transplanted APIs significantly reduced the peritoneal DO, approximately in a dose‐dependent manner. The number of viable islets and the insulin content per capsule decreased over time. Capsules retrieved from normoglycemic mice exhibited minimal host cell adherence. Conclusions Transplantation of encapsulated APIs can reduce peritoneal DO to severely hypoxic levels. Although normoglycemia could be maintained within the study period, the DO levels suggest that hypoxia is a factor contributing to loss of islet viability and insulin secretion with time in mice.