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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
- Source :
- Cancer Letters. 321:187-194
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- 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.
- Subjects :
- LICOFELONE
MAPK/ERK pathway
Cancer Research
Cell Survival
Membrane Fluidity
Blotting, Western
Fluorescent Antibody Technique
Apoptosis
COLON CANCER
Cell membrane
chemistry.chemical_compound
Cell Line, Tumor
Membrane fluidity
medicine
Humans
Pyrroles
Epidermal growth factor receptor
Kinase activity
Protein kinase B
EPIDERMAL GROWTH FACTOR RECEPTOR
biology
Anti-Inflammatory Agents, Non-Steroidal
Cell Membrane
Cell biology
ErbB Receptors
medicine.anatomical_structure
Oncology
chemistry
Colonic Neoplasms
Cancer research
biology.protein
Mitogen-Activated Protein Kinases
Signal transduction
Licofelone
Signal Transduction
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 321
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....d5cf5c8f29928450fd003acf93aa7cac