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.
Cancer Lett
; 321(2): 187-94, 2012 Aug 28.
Article
en En
| MEDLINE
| ID: mdl-22343320
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
1_doencas_nao_transmissiveis
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2_muertes_prematuras_enfermedades_notrasmisibles
/
6_colon_rectum_cancers
Asunto principal:
Pirroles
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Transducción de Señal
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Membrana Celular
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Supervivencia Celular
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Antiinflamatorios no Esteroideos
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Apoptosis
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Neoplasias del Colon
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Proteínas Quinasas Activadas por Mitógenos
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Receptores ErbB
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Fluidez de la Membrana
Límite:
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2012
Tipo del documento:
Article
País de afiliación:
Italia