Effect of free fatty acids and lysolipids on cellular uptake of doxorubicin in human breast cancer cell lines

Rasmussen, Nicolaj; Andersen, Jonas Hjelm; Jespersen, Henrik; Mouritsen, Ole G.; Ditzel, Henrik J.

doi:10.1097/cad.0b013e32833c2cf7

Cited by 17 publications

(12 citation statements)

References 9 publications

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“…When integrating into the lipid bilayer, the fatty acid increases the curvature stress which leads to more leaky membranes. A similar behavior has been found for a wide range of saturated and unsaturated fatty acids as well as lysolipids which have the opposite sense of curvature ( P <1) 39, 67–73. Lysolipids also promote drug release, although less dramatically, probably because they are more water soluble compared to a fatty acid with the same acyl chain.…”

Section: The Powerful Language Of Shapesupporting

confidence: 68%

Lipids, curvature, and nano‐medicine

Mouritsen

2011

Euro J Lipid Sci & Tech

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113

101

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The physical properties of the lamellar lipid-bilayer component of biological membranes are controlled by a host of thermodynamic forces leading to overall tensionless bilayers with a conspicuous lateral pressure profile and build-in curvature-stress instabilities that may be released locally or globally in terms of morphological changes. In particular, the average molecular shape and the propensity of the different lipid and protein species for forming non-lamellar and curved structures are a source of structural transitions and control of biological function. The effects of different lipids, sterols, and proteins on membrane structure are discussed and it is shown how one can take advantage of the curvature-stress modulations brought about by specific molecular agents, such as fatty acids, lysolipids, and other amphiphilic solutes, to construct intelligent drug-delivery systems that function by enzymatic triggering via curvature.Practical applications: The simple concept of lipid molecular shape and how it impacts on the structure of lipid aggregates, in particular the curvature and curvature stress in lipid bilayers and liposomes, can be exploited to construct liposome-based drug-delivery systems, e.g., for use as nano-medicine in cancer therapy. Non-lamellar-forming lysolipids and fatty acids, some of which may be designed to be prodrugs, can be created by phospholipase action in diseased tissues thereby providing for targeted drug release and proliferation of molecular entities with conical shape that break down the permeability barrier of the target cells and may hence enhance efficacy.

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Section: The Powerful Language Of Shapesupporting

confidence: 68%

Lipids, curvature, and nano‐medicine

Mouritsen

2011

Euro J Lipid Sci & Tech

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113

101

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“…An increase in cell membrane permeability would provide more chances for anti-cancer elements to pass though the cell membrane and maybe even intra-cellular membranes, such as the mitochondrial membrane (Rasmussen et al, 2010). The detection of cell membrane permeability indicated that HUVEC and LoVo had similar tendencies with additional LA, though the membrane permeability of the low concentration treatment was much higher than that of the high concentration treatment within the same group.…”

Section: Discussionmentioning

confidence: 93%

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

et al. 2010

J. Zhejiang Univ. Sci. B

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Polyunsaturated fatty acids (PUFAs) possess anti-cancer action both in vitro and in vivo. In the present study, we detected cell viability with methyl thiazolyl tetrazolium (MTT) assay and cell membrane permeability with propidium iodide (PI) fluorescence dyeing, and calculated cell membrane fluidity change as fluorescence anisotropy. Fatty acid content in cells was measured by gas chromatography/mass spectroscopy (GC/MS), and the relationship between fatty acid composition and cell viability was studied. We observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (≥300 µmol/L), while low concentrations (100-200 µmol/L) seemed to promote cell proliferation. Analyses of cell membrane permeability, cell membrane fluidity, and cell fatty acid composition suggested that the anti-cancer action of LA could be related to changes in the ratio of n-6 to n-3 PUFAs. We observed that pre-incubation of cancer cells with 100 µmol/L LA for 24 h enhanced cell sensitivity to the cytotoxic action of LA, whereas undifferentiated cell line LoVo seemed to have a distinct path in LA-induced death. These results showed that one of the mechanisms by which supplementation of LA induces cancer cell death could be altering the ratio of n-6/n-3 PUFAs, and this may be related to cell differentiation status.

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“…Loss of membrane integrity is one of the earliest indicators of cell damage and a sign of serious injury. It leads to cell death [30] most probably due to changes in the permeability and fluidity of the cell membrane as well as changes in cellular uptake and intracellular metabolism, shown to occur within hours [31]. In the present report we provide evidence that in vitro chemosensitivity testing of CETC using propidium iodide uptake, which results in nuclear red fluorescence, allows assessment, before treatment, of whether the tumor cells will be sensitive to the intended drugs.…”

Section: Introductionmentioning

confidence: 60%

“…So far, chemosensitivity testing has only been performed in cell cultures derived from primary tumors or cell lines [30,31], using methods such as proliferation assays and in vitro clonogenic assays, microfluidic approaches and multidrug resistance assays [32][33][34][35][36], cell metabolic activity assays [37][38][39], molecular assays to monitor expression of markers for responsiveness [40], and in vivo imaging assays [41]. These approaches, however, all have major drawbacks.…”

Section: Discussionmentioning

confidence: 99%

Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in <i>Vitro</i>: Correlation to in <i>Vivo</i> Sensitivity and Clinical Outcome

Rüdiger¹,

Stein²,

Schill³

et al. 2013

JCT

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Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empirically developed recommendations derived from statistical relapse rates occurring years after the treatment in the adjuvant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient's body for chemosensitivity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percentages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.

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Effect of free fatty acids and lysolipids on cellular uptake of doxorubicin in human breast cancer cell lines

Cited by 17 publications

References 9 publications

Lipids, curvature, and nano‐medicine

Lipids, curvature, and nano‐medicine

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in <i>Vitro</i>: Correlation to in <i>Vivo</i> Sensitivity and Clinical Outcome

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Effect of free fatty acids and lysolipids on cellular uptake of doxorubicin in human breast cancer cell lines

Cited by 17 publications

References 9 publications

Lipids, curvature, and nano‐medicine

Lipids, curvature, and nano‐medicine

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in &lt;i&gt;Vitro&lt;/i&gt;: Correlation to in &lt;i&gt;Vivo&lt;/i&gt; Sensitivity and Clinical Outcome

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Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in <i>Vitro</i>: Correlation to in <i>Vivo</i> Sensitivity and Clinical Outcome