Role of lipid-mobilising factor (LMF) in protecting tumour cells from oxidative damage


Lipid-mobilising factor (LMF) is produced by cachexia-inducing tumours and is involved in the degradation of adipose tissue, with increased oxidation of the released fatty acids through an induction of uncoupling protein (UCP) expression. Since UCP-2 is thought to be involved in the detoxification of free radicals if LMF induced UCP-2 expression in tumour cells, it might attenuate free radical toxicity. As a model system we have used MAC13 tumour cells, which do not produce LMF. Addition of LMF caused a concentration-dependent increase in UCP-2 expression, as determined by immunoblotting. This effect was attenuated by the β3 antagonist SR59230A, suggesting that it was mediated through a β3 adrenoreceptor. Co-incubation of LMF with MAC13 cells reduced the growth-inhibitory effects of bleomycin, paraquat and hydrogen peroxide, known to be free radical generators, but not chlorambucil, an alkylating agent. There was no effect of LMF alone on cellular proliferation. These results indicate that LMF antagonises the antiproliferative effect of agents working through a free radical mechanism, and may partly explain the unresponsiveness to the chemotherapy of cachexia-inducing tumours. © 2004 Cancer Research UK.

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Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
Additional Information: From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit To obtain permission to re-use content from this article visit RightsLink.
Uncontrolled Keywords: cachexia,free radicals,lipid mobilizing factor (LMF),uncoupling protein-2,Cancer Research,Oncology
Publication ISSN: 1532-1827
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.natu ... l/6601669a.html (Publisher URL)
PURE Output Type: Article
Published Date: 2004-03-22
Authors: Sanders, P.M.
Tisdale, Michael J.

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