Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells Gregorio-King, Claudia C., Gough, Tamara, Van Der Meer, Gavin J., Hosking, Jane B., Waugh, Caryll M., McLeod, Janet L., Collier, Fiona Mc and Kirkland, Mark A. 2004, Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells, Journal of steroid biochemistry and molecular biology, vol. 88, no. 3, pp. 311-320, doi: 10.1016/j.jsbmb.2003.12.007. Attached Files Name Description MIMEType Size Downloads Title Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells Author(s) Gregorio-King, Claudia C. Gough, Tamara Van Der Meer, Gavin J. Hosking, Jane B. Waugh, Caryll M. McLeod, Janet L. Collier, Fiona Mc orcid.org/0000-0002-5438-480X Kirkland, Mark A. Journal name Journal of steroid biochemistry and molecular biology Volume number 88 Issue number 3 Start page 311 End page 320 Total pages 10 Publisher Pergamon Place of publication Kidlington, England Publication date 2004-03 ISSN 0960-0760 Summary We have developed hematopoietic cells resistant to the cytotoxic effects of oxysterols. Oxysterol-resistant HL60 cells were generated by continuous exposure to three different oxysterols—25-hydroxycholesterol (25-OHC), 7-beta-hydroxycholesterol (7β-OHC) and 7-keto-cholesterol (7κ-C). We investigated the effects of 25-OHC, 7β-OHC, 7κ-C and the apoptotic agent staurosporine on these cells. The effect of the calcium channel blocker nifedipine on oxysterol cytotoxicity was also investigated. Differential display and real-time PCR were used to quantitate gene expression of oxysterol-sensitive and -resistant cells. Our results demonstrate that resistance to the cytotoxic effects of oxysterols is relatively specific to the type of oxysterol, and that the cytotoxicity of 25-OHC but not that of 7β-OHC and 7κ-C, appears to occur by a calcium dependent mechanism. Oxysterol-resistant cells demonstrated no significant difference in the expression of several genes previously implicated in oxysterol resistance, but expressed the bcl-2 gene at significantly lower levels than those observed in control cells. We identified three novel genes differentially expressed in resistant cells when compared to HL60 control cells. Taken together, the results of this study reveal potentially novel mechanisms of oxysterol cytotoxicity and resistance, and indicate that cytotoxicity of 25-OHC, 7β-OHC and 7κ-C occur by independent, yet overlapping mechanisms. Language eng DOI 10.1016/j.jsbmb.2003.12.007 Field of Research 110107 Metabolic Medicine Socio Economic Objective 970111 HERDC Research category C1.1 Refereed article in a scholarly journal Copyright notice ©2004, Elsevier Persistent URL http://hdl.handle.net/10536/DRO/DU:30025319 Document type: Journal Article Collections: Faculty of Health School of Medicine Related Links Link Description Connect to published version (restricted access) Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Mon, 15 Mar 2010, 10:04:38 EST Wed, 24 Mar 2010, 15:03:22 EST Mon, 29 Mar 2010, 21:45:58 EST Wed, 02 Nov 2011, 09:58:44 EST Tue, 22 Nov 2011, 08:50:49 EST Fri, 27 Sep 2013, 10:45:23 EST Fri, 27 Sep 2013, 10:45:58 EST Fri, 27 Sep 2013, 10:47:25 EST Fri, 22 Aug 2014, 15:34:01 EST Wed, 27 Aug 2014, 22:13:23 EST Tue, 14 Oct 2014, 07:43:31 EST Mon, 20 Oct 2014, 14:39:34 EST Filtered Full Citation counts:   Cited 18 times in TR Web of Science Cited 18 times in Scopus Search Google Scholar Access Statistics: 955 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Mon, 15 Mar 2010, 10:04:38 EST