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    Acyl chain length and charge effect on Tamoxifen-lipid model membrane interactions
    (Elsevier Science Bv, 2013) Bilge, Duygu; Kazanci, Nadide; Severcan, Feride
    Tamoxifen (TAM), which is an antiestrogenic agent, is widely used during chemotherapy of breast, pancreas, brain and liver cancers. In this study, TAM and model membrane interactions in the form of multilamellar vesicles (MLVs) were studied for lipids containing different acyl chain length and different charge status as a function of different TAM (1, 6, 9 and 15 mol%) concentrations. Zwitterionic lipids namely dipalmitoyl phosphatidylcholine (DPPC), and dimyristoylphosphatidylcholine (DMPC) lipids were used to see the acyl chain length effect and anionic dipalmitoyl phosphtidylglycerol (DPPG) lipid was used to see the charge effect. For this purpose Fourier transform-infrared (FTIR) spectroscopic and differential scanning calorimetric (DSC) techniques have been conducted. For zwitterionic lipid, concentration dependent different action of TAM was observed both in the gel and liquid crystalline phases by significantly increasing the lipid order and decreasing the dynamics for 1 mol% TAM, while decreasing the lipid order and increasing the dynamics of the lipids for higher concentrations (6, 9 and 15 mol%). However, different than neutral lipids, the dynamics and disorder of DPPG liposome increased for all TAM concentrations. The interactions between TAM and head group of multilamellar liposomes was monitored by analyzing the C=O stretching and PO2- antisymmetric double bond stretching bands. Increasing Tamoxifen concentrations led to a dehydration around these functional groups in the polar part of the lipids. DSC studies showed that for all types of lipids, TAM eliminates the pre-transition, shifts the main phase transition to lower temperatures and broadened the phase transition curve. The results indicate that not the acyl chain length but the charge status of the polar head group induces different effects on lipid membranes order and dynamics. (C) 2013 Elsevier B.V. All rights reserved.
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    Concentration dependent different action of tamoxifen on membrane fluidity
    (Springer/Plenum Publishers, 2007) Kazanci, Nadide; Severcan, Feride
    Tamoxifen (TAM) is a non-steroidal antiestrogen drug, which is widely used to prevent and treat breast, liver, pancreas and brain cancers. The present work investigates, in detail, the concentration dependent behavior of TAM (varying from 1 mol% to 45 mol%) on membrane fluidity. The differential scanning calorimetry (DSC) studies showed that tamoxifen eliminates the pre-transition and decreases the main phase transition to lower temperatures. Using visible spectroscopy at 440 nm and Fourier transform infrared (FTIR) spectroscopy it was found that membrane dynamics decreases for 1 and 3 mol% tamoxifen in both the gel and liquid crystalline phases. Above these concentrations up to 18-24 mol%, it increases and reaches its maximum values. As tamoxifen concentration was further increased, the membrane dynamics is found to be gradually decreased, although TAM still has fluidifying effect in comparison to pure phospholipid membrane. These findings are important for the effective use of tamoxifen in the cancer therapy to eliminate its dose dependent side effects reported in the literature.
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    Concentration-dependent effect of melatonin on DSPC membrane
    (Elsevier, 2013) Sahin, Ipek; Bilge, Duygu; Kazanci, Nadide; Severcan, Feride
    The concentration-induced effects of melatonin on distearoyl phosphatidylcholine (DSPC) model membranes were investigated by using two different non-invasive techniques, namely Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). An investigation of the C-H, C=O and PO2- double bond stretching mode in FTIR spectra and DSC studies reveals that the inclusion of melatonin changes the physical properties of the DSPC multilamellar liposomes (MLVs) by shifting the main phase transition to lower temperatures, abolishing the pretransition, ordering the system in the gel phase and slightly disordering the system in the liquid crystalline phase, increasing the dynamics both in the gel phase and liquid crystalline phases. Melatonin also causes strong hydrogen bonding between C=O and PO2- groups of lipids and the water molecules around. (C) 2013 Elsevier B.V. All rights reserved.
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    Interactions of tamoxifen with distearoyl phosphatidylcholine multilamellar vesicles: FTIR and DSC studies
    (Pergamon-Elsevier Science Ltd, 2014) Bilge, Duygu; Sahin, Ipek; Kazanci, Nadide; Severcan, Feride
    Interactions of a non-steroidal antiestrogen drug, tamoxifen (TAM), with distearoyl-sn-glycero-3-phosphatidylcholine (DSPC) multilamellar liposomes (MLVs) were investigated as a function of drug concentration (1-15 mol%) by using two noninvasive techniques, namely Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). FTIR spectroscopy results show that increasing TAM concentrations (except 1 mol%) increased the wavenumbers of the CH2 stretching modes, implying an disordering effect for DSPC MLVs both in the gel and liquid crystalline phases. The bandwidth values of the CH2 stretchings except for I mol% increased when TAM concentrations increased for DSPC liposomes, indicating an increase in the dynamics of liposomes. The C=O stretching and PO2- antisymmetric double bond stretching bands were analyzed to study interactions of TAM with head groups of lipids. As the concentrations of TAM increased, dehydration occurred around these functional groups in the polar part of the lipids. The DSC studies on thermal properties of DSPC lipids indicate that TAM eliminated the pre transition, shifted the main phase transition to lower temperatures and broadened the phase transition curve of the liposomes. (C) 2014 Elsevier B.V. All rights reserved.
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    Melatonin induces opposite effects on order and dynamics of anionic DPPG model membranes
    (Elsevier Science Bv, 2007) Sahin, Ipek; Severcan, Feride; Kazanci, Nadide
    The temperature and concentration induced effects of melatonin on anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar liposomes (MLVs) were investigated by using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The results show that melatonin does not perturb the phase transition profile, while a decrease in the main transition temperature (T-m) is noticed at high melatonin concentrations (15, 24 and 30 mol Low concentrations of melatonin (3, 6 and 9 mol %) decrease the frequency of the CH2 stretching mode, implying an ordering effect, whilst high concentrations of melatonin disorders system both in the gel and liquid crystalline phases. Furthermore, at low and high concentrations, melatonin also causes opposite effect on membrane dynamics. The bandwidth of the CH2 stretching modes decreases at low concentrations, implying a decrease in the dynamics, while increasing it at high concentrations. Furthermore, it causes significant decrease in the frequency of the C=O stretching and PO2- antisymmetric double bond stretching bands of DPPG for all concentrations both in the gel and liquid crystalline phases, which indicates strong hydrogen bonding around these functional groups. (C) 2006 Elsevier B.V. All rights reserved.