Journal
CANCER LETTERS
Volume 321, Issue 2, Pages 187-194Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.02.003
Keywords
Colon cancer; Licofelone; Membrane fluidity; Epidermal growth factor receptor; Apoptosis
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Funding
- Fundamental Oriented Research (RFO), Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Fondazione Cassa di Risparmio in Bologna
- Fondazione Banca del Monte e Ravenna
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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 (MARK) 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. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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