HERG K+ channel expression-related chemosensitivity in cancer cells and its modulation by erythromycin

Chen, Shuzhen; Jiang, Min; Zhen, Yong‐Su

doi:10.1007/s00280-004-0960-5

Cited by 70 publications

(54 citation statements)

References 21 publications

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“…Chen et al (28) reported that A549 cells expressing low levels of HERG were less sensitive than HT-29 cells expressing high levels of HERG to vincristine, paclitaxel and hydroxy-camptothecin. The chemosensitivities of HERG-transfected A549 cells to vincristine, paclitaxel and hydroxy-camptothecin were significantly increased, compared to parent A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Human ether-ï¿½-go-go-related gene expression is essential for cisplatin to induce apoptosis in human gastric cancer

Shen

2011

Oncol Rep

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Abstract. Human ether-à-go-go-related gene (HERG) is overexpressed in a wide range of human cancers and regulates survival, migration, and apoptosis. The aim of this study was to investigate the role of HERG in cisplatin-induced apoptosis in gastric cancer in vitro and in vivo. siRNA was used to silence HERG expression. HERG expression was detected by Western blot analysis in vitro, and further confirmed by immunohistochemistry in vivo. Chemosensitivity to cisplatin in gastric cancer cells was analyzed with a Cell Counting Kit-8 assay. Apoptosis was detected by flow cytometry in vitro, and in situ apoptotic SGC7901 human gastric tumor cells in BALB/c nude mice were detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Our results show that cisplatin increased the expression of HERG in gastric cancer cells. Silencing HERG inhibited the apoptosis induced by cisplatin both in vitro and in vivo, by attenuating the cisplatin effects on Bcl-2, Bax and active caspase-3. The role of HERG in modulation of cisplatin-induced apoptosis suggests that HERG may provide a new potential target for cisplatin chemotherapy in human gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Human ether-ï¿½-go-go-related gene expression is essential for cisplatin to induce apoptosis in human gastric cancer

Shen

2011

Oncol Rep

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“…The human ether-a-go-go related gene (HERG) that encodes a delayed rectifier K + channel was shown to promote H 2 O 2 -induced apoptosis in a variety of tumor cells expressing this channel, in direct contrast to cells that lacked HERG expression [51]. Additionally, cell lines with high HERG potassium channel expression have been shown to be more sensitive to chemotherapeutic drugs than cells with a lower HERG expression [52]. Over-expression of HERG in low expressing cells resulted in an increase in sensitivity to drug treatment, again suggesting that potassium channels can be major players for the control and/or activation of apoptosis.…”

Section: Potassium Channels In Apoptosismentioning

confidence: 99%

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

Bortner

Cidlowski

2007

Archives of Biochemistry and Biophysics

230

193

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The loss of cell volume or cell shrinkage has been a morphological hallmark of the programmed cell death process known as apoptosis. This isotonic loss of cell volume has recently been term apoptotic volume decrease or AVD to distinguish it from inherent volume regulatory responses that occurs in cells under anisotonic conditions. Recent studies examining the intracellular signaling pathways that result in this unique cellular characteristic have determined that a fundamental movement of ions, particularly monovalent ions, underlie the AVD process and plays an important role on controlling the cell death process. An efflux of intracellular potassium was shown to be a critical aspect of the AVD process, as preventing this ion loss could protect cells from apoptosis. However, potassium plays a complex role as a loss of intracellular potassium has also been shown to be beneficial to the health of the cell. Additionally, the mechanisms that a cell employs to achieve this loss of intracellular potassium vary depending on the cell type and stimulus used to induce apoptosis, suggesting multiple ways exist to accomplish the same goal of AVD. Additionally, sodium and chloride have been shown to play a vital role during cell death in both the signaling and control of AVD in various apoptotic model systems. This review examines the relationship between this morphological change and intracellular monovalent ions during apoptosis.

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“…Osteogenic Sarcoma ↑E2F-1 Transfection No change Sensitive [30] E2F-1(transcription factor) cyclin B1 levels and cdc2 kinase activity becoming sensitive to paclitaxel A549 Lung ↑HERG Transfection 0.875 0.039 [31] Potassium Channel, mechanism of paclitaxel sensitivity unknown SH-EP Neuroblastoma ↑MYCN Transfection 0.94 0.51 [32] Mechanism of paclitaxel sensitivity not studied [33] ↓BRCA1 leads to transcriptional modifications of the JNK pathway ↑JNK1 ↓JNK2 MCF-10A…”

Section: Genetic Modifications Which Induce the Inverse Cisplatin/pacmentioning

confidence: 99%

A Systematic Review of Genes Involved in the Inverse Resistance Relationship Between Cisplatin and Paclitaxel Chemotherapy: Role of BRCA1

Stordal¹,

Davey

2009

CCDT

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A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel [1] . Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the inverse resistance relationship as well as potential markers for monitoring the development of resistance in the clinical treatment of cancer. The literature search revealed 91 genetically modified cell lines which report toxicity or viability/apoptosis data for cisplatin and paclitaxel relative to their parental cell lines. This resulted in 26 genes being associated with the inverse cisplatin/paclitaxel phenotype. The gene with the highest number of genetically modified cell lines associated with the inverse resistance relationship was BRCA1 and this gene is discussed in detail with reference to chemotherapy response in cell lines and in the clinical treatment of breast, ovarian and lung cancer. Other genes associated with the inverse resistance phenotype included dihydrodiol dehydrogenase (DDH) and P-glycoprotein. Genes which caused cross resistance or cross sensitivity between cisplatin and paclitaxel were also examined, the majority of these genes were apoptosis associated genes which may be useful for predicting cross resistance. We propose that BRCA1 should be the first of a panel of cellular markers to predict the inverse cisplatin/paclitaxel resistance phenotype.3

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HERG K+ channel expression-related chemosensitivity in cancer cells and its modulation by erythromycin

Abstract: HERG expression levels and chemosensitivity were positively correlated for vincristine, paclitaxel, and hydroxy-camptothecin. Erythromycin was active as a modulator. These results suggest that HERG may serve as a molecular marker and modulating target for individualized cancer therapy.

Cited by 70 publications

References 21 publications

Human ether-ï¿½-go-go-related gene expression is essential for cisplatin to induce apoptosis in human gastric cancer

Human ether-ï¿½-go-go-related gene expression is essential for cisplatin to induce apoptosis in human gastric cancer

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

A Systematic Review of Genes Involved in the Inverse Resistance Relationship Between Cisplatin and Paclitaxel Chemotherapy: Role of BRCA1

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