Abstract
The effects of different concentrations of celecoxib on the acyl chain order, dynamics and the hydration status of the head group and interfacial region of model membranes containing DSPC and cholesterol were investigated in detail using Fourier transform infrared spectroscopy. Our results reveal that regardless of the presence of cholesterol, celecoxib is able to alter the physical properties of membranes. It exerts opposing effects on membrane order at high and low concentrations and decreases membrane fluidity in the presence of cholesterol. An evidence of phase separation has also been observed. The decrease in membrane fluidity supports the hypothesis that celecoxib may induce changes in the activity of membrane bound enzymes through modulating physical properties of the membrane thereby contributing to its anticancer activity. A possible change in the location of celecoxib in DSPC membranes when cholesterol is present has also been proposed. These results clarify, to a certain extent, the molecular interactions of celecoxib with membrane systems and may additionally contribute to a better understanding of COX-2 independent mechanisms of celecoxib action.
Highlights
Cyclooxygenases (COX), called prostaglandin H synthases (PGHS), are enzymes localized at the nuclear or endoplasmic reticulum membrane of eukaryotic cells
In our previous study, using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC), we have found that CLX exerts opposing effects on membrane order in a concentration dependent manner and it decreases the fluidity of the membrane at all concentrations
FTIR spectroscopy was used to determine the changes in membrane structure and dynamics in response to low and high concentrations of CLX by analyzing the frequency and bandwidth of different vibrational modes which represent the acyl chains, head group and interfacial region of lipid molecules [5,26]
Summary
Cyclooxygenases (COX), called prostaglandin H synthases (PGHS), are enzymes localized at the nuclear or endoplasmic reticulum membrane of eukaryotic cells. These are the key enzymes of the eicosanoid cascade which can convert arachidonic acid to prostaglandins. COX-2, is not constitutively expressed in most tissues with the exception of kidney and brain [9]. This isoform can be induced by a number of stimuli, such as bacterial lipopolysaccharide (LPS), interleukin-1 and 2, and tumor necrosis factor (TNF)-α, all of which are related to inflammation [9]. The induction of COX-2 by inflammatory mediators led investigators to label this enzyme as pathological [28]
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