Differentially expressed proteins in human breast cancer cells sensitive and resistant to paclitaxel

Pavlíková, Nela; Bartoňová, Irena; Dincakova, Lucia; Halada, Petr; Kovář, Jan

doi:10.3892/ijo.2014.2484

Cited by 7 publications

(7 citation statements)

References 70 publications

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“…To verify the causal link between ABCB1 overexpression and the origin of PDT resistance derived from KP1 and KP6 porphyrins, we investigated cells with acquired MDR resistance to paclitaxel strongly overexpressing ABCB12223. Paclitaxel-resistant cells MCF-7/PacR were loaded with PS and their fluorescence and phototoxicity after light exposure was evaluated and compared to parental paclitaxel-sensitive MCF-7 cells.…”

Section: Resultsmentioning

confidence: 99%

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Králová

Kolář

Kahle

et al. 2017

Sci Rep

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The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design.

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Section: Resultsmentioning

confidence: 99%

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Králová

Kolář

Kahle

et al. 2017

Sci Rep

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“…Both resistant sublines overexpress multi-drug resistance transporters ABCB1 and ABCC3 (Němcová-Furstová et al, 2016). Moreover, both sublines also express other proteins which may be involved in resistance to paclitaxel (Pavlíková et al, 2014, Pavlíková et al, 2015). Our previous results have showed that novel taxanes with modified structures, especially at the C′3 and C3′N positions (Jelínek et al, 2013, Kovář et al, 2009, Vobořilová et al, 2011), were able to overcome paclitaxel resistance and induced cell death in tested paclitaxel-resistant breast cancer sublines (Němcová-Furstová et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Substituents at the C3′ and C3′N positions are critical for taxanes to overcome acquired resistance of cancer cells to paclitaxel

Jelínek

Balušíková

Daniel

et al. 2018

Toxicology and Applied Pharmacology

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We tested the role of substituents at the C3' and C3'N positions of the taxane molecule to identify taxane derivatives capable of overcoming acquired resistance to paclitaxel. Paclitaxel-resistant sublines SK-BR-3/PacR and MCF-7/PacR as well as the original paclitaxel-sensitive breast cancer cell lines SK-BR-3 and MCF-7 were used for testing. Increased expression of the ABCB1 transporter was found to be involved in the acquired resistance. We tested three groups of taxane derivatives: (1) phenyl group at both C3' and C3'N positions, (2) one phenyl at one of the C3' and C3'N positions and a non-aromatic group at the second position, (3) a non-aromatic group at both C3' and C3'N positions. We found that the presence of phenyl groups at both C3' and C3'N positions is associated with low capability of overcoming acquired paclitaxel resistance compared to taxanes containing at least one non-aromatic substituent at the C3' and C3'N positions. The increase in the ATPase activity of ABCB1 transporter after the application of taxanes from the first group was found to be somewhat higher than after the application of taxanes from the third group. Molecular docking studies demonstrated that the docking score was the lowest, i.e. the highest binding affinity, for taxanes from the first group. It was intermediate for taxanes from the second group, and the highest for taxanes from the third group. We conclude that at least one non-aromatic group at the C3' and C3'N positions of the taxane structure, resulting in reduced affinity to the ABCB1 transporter, brings about high capability of taxane to overcome acquired resistance of breast cancer cells to paclitaxel, due to less efficient transport of the taxane compound out of the cancer cells.

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“…2DE was performed as described previously . Briefly, an IPGphor focusing unit (GE Healthcare, Uppsala, Sweden) was used for isoelectric focusing of samples loaded on 7 cm long, pH 3–11 Immobiline DryStrips (GE Healthcare, Uppsala, Sweden).…”

Section: Methodsmentioning

confidence: 99%

Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

Němcová‐Fürstová

Balušíková

Halada

et al. 2019

Proteomics Clinical Apps

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Purpose: Lipotoxicity is implicated in type 2 diabetes pathogenesis. Its molecular mechanisms are not completely understood. The aim of this study is to identify new suspect proteins involved in pancreatic ␤-cell death induction by saturated fatty acids and its inhibition by unsaturated fatty acids. Experimental design: Employing 2DE analysis and subsequent western blot confirmation, the differences in membrane/membrane-associated protein expression in human ␤-cell line NES2Y are assessed during cell death induction by stearate and its inhibition by oleate. Results: Induction of apoptosis by stearate is associated with significantly increased levels of Hsp90␤, peroxiredoxin-1, and 14-3-3␥ in the membrane fraction of NES2Y cells and significantly decreased levels of annexin A2, annexin A4, and reticulocalbin-2. All these changes are significantly inhibited by oleate co-application. No expression changes are detected after application of stearate together with oleate. Furthermore, the expression of reticulocalbin-2 is significantly decreased after stearate application also in the whole cell lysate. Conclusions and clinical relevance: Several membrane-associated proteins that could be related to pro-and anti-apoptotic signaling initiated by fatty acids in human pancreatic ␤-cells are identified. As far as we know, annexin A4, reticulocalbin-2, and 14-3-3␥ represent novel molecules related to the effect of fatty acids on ␤-cell viability.

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Differentially expressed proteins in human breast cancer cells sensitive and resistant to paclitaxel

Cited by 7 publications

References 70 publications

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Substituents at the C3′ and C3′N positions are critical for taxanes to overcome acquired resistance of cancer cells to paclitaxel

Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

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