| The decrease of cell membrane fluidity by the non-steroidal anti-inflammatory drug Licofelone inhibits epidermal growth factor receptor signalling and triggers apoptosis in HCA-7 colon cancer cells. | |
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MedLine Citation:
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PMID: 22343320 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The ability to induce changes in cell membrane properties is nowadays considered an additional mechanism to explain the pharmacological effects of non-steroidal anti-inflammatory drugs (NSAIDs). We previously demonstrated that the NSAID Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, triggers apoptosis in HCA-7 colon cancer cells independently from the inhibition of these enzymes. Here, we provide evidence that, in HCA-7 cells, the pro-apoptotic effect of this drug relies, at least in part, on its ability to inhibit epidermal growth factor receptor (EGFR) signalling by a decrease of cell membrane fluidity. Indeed, Licofelone induced a relevant change in the relative proportions of some saturated, monounsaturated and polyunsaturated fatty acids constituting HCA-7 phospholipid fraction, and significantly increased the levels of cholesterol in HCA-7 cell membrane. All of these changes resulted in a remarkable decrease of membrane fluidity. Such phenomenon was associated with the block of EGFR kinase activity and of its downstream targets, the p44-42 mitogen-activated protein kinase (MAPK) and AKT cascades, whose inhibitions were found to induce apoptosis in HCA-7 cells. Overall, these findings provide a new additional mechanism by which NSAIDs are effective toward colon cancer cells. |
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Authors:
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Simona Tavolari; Alessandra Munarini; Gianluca Storci; Stefan Laufer; Pasquale Chieco; Tiziana Guarnieri |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-14 |
Journal Detail:
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Title: Cancer letters Volume: - ISSN: 1872-7980 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Center for Applied Biomedical Research (C.R.B.A.), Sant'Orsola-Malpighi University Hospital, Bologna, Italy. |
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