Cisplatin Rapidly Down-regulates Its Own Influx Transporter hCTR1 in Cultured Human Ovarian Carcinoma Cells

@article{Holzer2004CisplatinRD,
  title={Cisplatin Rapidly Down-regulates Its Own Influx Transporter hCTR1 in Cultured Human Ovarian Carcinoma Cells},
  author={Alison Kay Holzer and Kuniyuki Katano and Leo W. J. Klomp and Stephen B. Howell},
  journal={Clinical Cancer Research},
  year={2004},
  volume={10},
  pages={6744 - 6749}
}
Purpose: Cisplatin (DDP)-resistant cells commonly exhibit reduced drug accumulation. Previous studies have shown that the major copper (Cu) influx transporter CTR1 controls the uptake of DDP in yeast and mammalian cells. The goal of this study was to examine the effect of Cu and DDP on the level and subcellular localization of hCTR1 protein in human ovarian carcinoma cells. Experimental Design: Cultured human ovarian carcinoma A2780 cells were exposed to DDP and Cu, and the effect on hCTR1 was… 

Figures from this paper

The internalization and degradation of human copper transporter 1 following cisplatin exposure.
TLDR
It is confirmed that DDP triggers the rapid loss of hCTR1 from ovarian carcinoma cells at clinically relevant concentrations and the results indicate that D DP-induced loss of HCTR 1 involves internalization from the plasma membrane by macropinocytosis followed by proteasomal degradation.
Enhanced Delivery of Cisplatin to Intraperitoneal Ovarian Carcinomas Mediated by the Effects of Bortezomib on the Human Copper Transporter 1
TLDR
Proteasomal inhibition prevented cisplatin-induced down-regulation of hCTR1 in ovarian cancer cells and enhanced drug uptake and cell killing in a synergistic manner.
The Copper Influx Transporter Human Copper Transport Protein 1 Regulates the Uptake of Cisplatin in Human Ovarian Carcinoma Cells
TLDR
Although increased expression of h CTR1 mediates greater cellular accumulation of copper and cisplatin, hCTR1 delivers these compounds into intracellular compartments from which they do not have ready access to their key cytotoxic targets.
Regulation of Copper Transporter 2 Expression by Copper and Cisplatin in Human Ovarian Carcinoma Cells
TLDR
Comparison of the ability of copper and DDP to modulate the expression of CTR1 in ATOX1(+/+) and ATOx1(−/−) indicated that ATOX 1 participates in the regulation of CTR2 expression, which is regulated by copper availability via the copper-dependent regulator ATOX2.
Correction: EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer
TLDR
It is demonstrated for the first time that (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice and uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.
EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer
TLDR
It is demonstrated for the first time that (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice and uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.
A Re-Evaluation of the Role of hCTR1, the Human High-Affinity Copper Transporter, in Platinum-Drug Entry into Human Cells
TLDR
It is shown that hCTR1 is not the major entry route of platinum drugs, and that the copper transporter is not internalized in response to extracellular drug, suggesting the major Entry pathway for platinum drugs is not saturable at relevant concentrations and not protein-mediated.
The regulation of the human copper transporter 1 and its role in the cellular uptake of Cisplatin - eScholarship
TLDR
The experiments described in the following work demonstrate that hCTR1 plays a role in the transport of cisplatin, as alterations of h CTR1 protein levels correspond to platinum accumulation levels.
Comparison between copper and cisplatin transport mediated by human copper transporter 1 (hCTR1).
TLDR
Results demonstrated that the cells expressing the hCTR1 mutants of histidine-rich motifs in the N-terminus resulted in a higher basal copper level in the steady state compared to those expressing wild-type protein, suggesting that this motif is crucial for the function of the transporter.
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