scholarly journals Ion channels and transporters in the development of drug resistance in cancer cells

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130109 ◽  
Author(s):  
Else K. Hoffmann ◽  
Ian H. Lambert
Keyword(s):  
Drug Resistance ◽  
Ion Channels ◽  
Drug Uptake ◽  
Multi Drug Resistance ◽  
Drug Efflux ◽  
Ion Transporters ◽  
Drug Induced ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration

Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion transporters is the main focus of this paper and we demonstrate how pro-apoptotic ion channels are downregulated, while anti-apoptotic ion transporters are upregulated in MDR. We also discuss whether upregulation of ion transport proteins that are important for proliferation contribute to MDR. Finally, we discuss the possibility that the development of MDR involves sequential and localized upregulation of ion channels involved in proliferation and migration and a concomitant global and persistent downregulation of ion channels involved in apoptosis.

scholarly journals The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration

2011 ◽  
Vol 22 (17) ◽  
pp. 3032-3040 ◽  
Author(s):  
Aichi Msaki ◽  
Ana M. Sánchez ◽  
Li Fang Koh ◽  
Benjamin Barré ◽  
Sonia Rocha ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cellular Migration ◽  
Negative Regulator ◽  
Drug Induced ◽  
Conserved Residues ◽  
Cellular Processes ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela−/−mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function. These include previously described effects on chemotherapeutic drug-induced apoptosis, as well as new roles for this modification in autophagy, cell proliferation, and migration. This last effect was associated with alterations in the actin cytoskeleton and expression of cellular migration–associated genes such as WAVE3 and α-actinin 4. We also define a new component of cisplatin-induced, RelA T505–dependent apoptosis, involving induction of NOXA gene expression, an effect explained at least in part through induction of the p53 homologue, p73. Therefore, in contrast to other RelA phosphorylation events, which positively regulate NF-κB function, we identified RelA T505 phosphorylation as a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration.

Transcription factor 3 controls cell proliferation and migration in glioblastoma multiforme cell lines

2016 ◽  
Vol 94 (3) ◽  
pp. 247-255 ◽  
Author(s):  
Ruiting Li ◽  
Yinghui Li ◽  
Xin Hu ◽  
Haiwei Lian ◽  
Lei Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Normal Brain ◽  
Phosphatidylinositol 3 Kinase ◽  
T Cell Factor ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration ◽  
Transcription Factor 3

Transcription factor 3 (TCF3) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family. Recent studies have demonstrated its potential carcinogenic properties. Here we show that TCF3 was upregulated in glioma tissues compared with normal brain tissues. This upregulation of the TCF3 gene probably has functional significance in brain-tumor progression. Our studies on glioblastoma multiforme (GBM) cell lines show that knock-down of TCF3 induced apoptosis and inhibited cell migration. Further analysis revealed that down-regulation of TCF3 gene expression inhibits Akt and Erk1/2 activation, suggesting that the carcinogenic properties of TCF3 in GBM are partially mediated by the phosphatidylinositol 3-kinase–Akt and MAPK–Erk signaling pathways. Considered together, the results of this study demonstrate that high levels of TCF3 in gliomas potentially promote glioma development through the Akt and Erk pathways.

scholarly journals Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 761 ◽  
Author(s):  
Roberta Peruzzo ◽  
Ildiko Szabo
Keyword(s):  
Ion Channels ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Cytochrome C Release ◽  
Drug Induced ◽  
Point Of No Return ◽  
Different Types ◽  
Subsequent Activation ◽  
Induced Apoptosis ◽  
Potential Efficiency

Mitochondrial ion channels are emerging oncological targets, as modulation of these ion-transporting proteins may impact on mitochondrial membrane potential, efficiency of oxidative phosphorylation and reactive oxygen production. In turn, these factors affect the release of cytochrome c, which is the point of no return during mitochondrial apoptosis. Many of the currently used chemotherapeutics induce programmed cell death causing damage to DNA and subsequent activation of p53-dependent pathways that finally leads to cytochrome c release from the mitochondrial inter-membrane space. The view is emerging, as summarized in the present review, that ion channels located in this organelle may account in several cases for the resistance that cancer cells can develop against classical chemotherapeutics, by preventing drug-induced apoptosis. Thus, pharmacological modulation of these channel activities might be beneficial to fight chemo-resistance of different types of cancer cells.

scholarly journals Acid-sensing ion channels contribute to the effect of extracellular acidosis on proliferation and migration of A549 cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831770575 ◽  
Author(s):  
Yu Wu ◽  
Bo Gao ◽  
Qiu-Ju Xiong ◽  
Yu-Chan Wang ◽  
Da-Ke Huang ◽  
...  
Keyword(s):  
Ion Channels ◽  
A549 Cells ◽  
Extracellular Acidosis ◽  
Acid Sensing Ion Channels ◽  
And Migration ◽  
Proliferation And Migration

Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy

2003 ◽  
Vol 31 (6) ◽  
pp. 1372-1377 ◽  
Author(s):  
P.J. Thornalley
Keyword(s):  
Drug Resistance ◽  
Excision Repair ◽  
Glyoxalase I ◽  
Drug Induced ◽  
Antitumour Agents ◽  
Lung Carcinoma Cells ◽  
Antitumour Agent ◽  
A Cell ◽  
Base Excision ◽  
Induced Apoptosis

Glycation of nucleotides in DNA forms AGEs (advanced glycation end-products). Nucleotide AGEs are: the imidazopurinone derivative dG-G {3-(2´-deoxyribosyl)-6,7-dihydro-6,7-dihydroxyimidazo[2,3-b]purin-9(8)one}, CMdG (N2-carboxymethyldeoxyguanosine) and gdC (5-glycolyldeoxycytidine) derived from glyoxal, dG-MG {6,7-dihydro-6,7-dihydroxy-6-methylimidazo-[2,3-b]purine-9(8)one}, dG-MG2 [N2,7-bis-(1-hydroxy-2-oxopropyl)deoxyguanosine] and CEdG [N2-(1-carboxyethyl)deoxyguanosine] derived from methylglyoxal, and dG-3DG [N2-(1-oxo-2,4,5,6-tetrahydroxyhexyl)deoxyguanosine] derived from 3-deoxyglucosone and others. Glyoxal and methylglyoxal induce multi-base deletions, and base-pair substitutions – mostly occurring at G:C sites with G:C→C:G and G:C→T:A transversions. Suppression of nucleotide glycation by glyoxalase I and aldehyde reductases and dehydrogenases, and base excision repair, protects and recovers DNA from damaging glycation. The effects of DNA glycation may be most marked in diabetes and uraemia. Mutations arising from DNA glycation may explain the link of non-dietary carbohydrate intake to incidence of colorectal cancer. Overexpression of glyoxalase I was found in drug-resistant tumour cells and may be an example of an undesirable effect of the enzymatic protection against DNA glycation. Experimental overexpression of glyoxalase I conferred resistance to drug-induced apoptosis. Glyoxalase I-mediated drug resistance was found in human leukaemia and lung carcinoma cells. Methylglyoxal-mediated glycation of DNA may contribute to the cytotoxicity of some antitumour agents as a consequence of depletion of NAD+ by poly(ADP-ribose) polymerase, marked increases in triosephosphate concentration and increased formation of methylglyoxal. S-p-Bromobenzylglutathione cyclopentyl diester is a cell-permeable glyoxalase I inhibitor. It countered drug resistance and was a potent antitumour agent against lung and prostate carcinoma. Glyoxalase I overexpression was also found in invasive ovarian cancer and breast cancer.

scholarly journals Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance

Oncogene ◽  
2001 ◽  
Vol 20 (22) ◽  
pp. 2749-2760 ◽  
Author(s):  
Katrin Friedrich ◽  
Thomas Wieder ◽  
Clarissa Von Haefen ◽  
Silke Radetzki ◽  
Reiner Jänicke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Caspase 3 ◽  
Breast Cancer Cell Lines ◽  
Drug Induced ◽  
Acquired Drug Resistance ◽  
Induced Apoptosis
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