Mechanistic basis of a combination d-penicillamine and platinum drugs synergistically inhibits tumor growth in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

Chen, Szu Jung; Kuo, Ching Chuan; Pan, Hsin Yi; Tsou, Tsui‐Chun; Yeh, Szu Ching; Chang, Jang Yang

doi:10.1016/j.bcp.2015.03.006

Cited by 35 publications

(31 citation statements)

References 33 publications

(39 reference statements)

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“…In our previous study, we demonstrated that a copper-chelating agent could reverse oxaliplatin resistance through the regulation of the copper importer hCtr1 and exporter ATP7A [14]. We further observed that the expression level of TfR1 was lower in S3 cells than in parental cells (Figure 2A).…”

Section: Discussionmentioning

confidence: 66%

“…As presented in Figure 2B, desferal treatment significantly reduced more intracellular iron and copper concentrations in S3 cells than in SiHa cells (48% vs.17%, P = 0.019; 96% vs.69%, P = 0.012). Previously, we demonstrated that the expression of hCtr1 is controlled by the transcription factor Sp1, which is negatively regulated by intracellular copper concentrations [14]. We further evaluated the effect of desferal on the expression of Sp1 and hCtr1 in both SiHa and S3 cells.…”

Section: Resultsmentioning

confidence: 99%

“…We and others have demonstrated that the decreased expression of hCtr1 and overexpression of ATP7A and ATP7B have a crucial role in the development of platinum resistance [10–14]. Moreover, our previous study reported that combination of D-penicillamine, a copper chelator, and platinum drugs exhibits synergistic interaction in oxaliplatin-resistant cancer cells through modulation of hCtr1 and ATP7A expression [13, 14]. Thus, we proposed that the metal chelators, such as iron chelators, may also be benefit in manipulation of copper transporters and sensitize resistant cancer cells with chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

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Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

et al. 2016

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The development of resistance to platinum drugs in cancer cells severely reduces the efficacy of these drugs. Thus, the discovery of novel drugs or combined strategies to overcome drug resistance is imperative. In addition to our previous finding that combined D-penicillamine with platinum drugs exerts synergistic cytotoxicity, we recently identified a novel therapeutic strategy by combining an iron chelating agent desferal with platinum drugs to overcome platinum resistance in an oxaliplatin-resistant human cervical cancer cell line, S3. Further study demonstrated that the level of platinum–DNA adduct formation positively correlated with cell death in combination of desferal with platinums than that of each drug alone in S3 cells. Decrement of human copper transporter 1 (hCtr1) and transferrin receptor 1 (TfR1) expression involved in the development of platinum resistance in S3 cells. Moreover, desferal promoted the expression of hCtr1 through the upregulation of Sp1. The overexpression of Sp1 increased the expression of NF-κB and translocated it into the nucleus to bind to the TfR1 promoter region, which subsequently increased the expression of TfR1. Importantly, the cotreatment of oxaliplatin with desferal significantly potentiated the oxaliplatin-elicited antitumoral effect in the oxaliplatin-resistant xenograft animal model without any toxic effect observed. Taken together, these results demonstrated that the combination of desferal with oxaliplatin can overcome oxaliplatin resistance through the regulation of hCtr1 and TfR1, and may have beneficial effect for treatment of patient with oxaliplatin-refractory tumors.

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Section: Discussionmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

et al. 2016

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“…In a recent ICP-MS based preclinical study, Chen et al showed that the combination of d -penicillamine with oxaliplatin or cisplatin led to an increase in platinum-adduct formation and cytotoxicity in the resistant cervical carcinoma cell line. 63 Similarly, Jiang et al reported increased carboplatin-DNA adduct formation and cytotoxicity in an urothelial carcinoma cell line when cotreated with paclitaxel. 90 However, the in vivo contribution of each individual drug in a regimen to tumor response is more complicated to delineate than in cell culture cytotoxicity experiments.…”

Section: Platinum Drugs and Combination Therapiesmentioning

confidence: 94%

“…60−63 Compared to the methods described above, ICP-MS has high throughput with less tedious procedures and may be amenable to clinical studies. 64 Its ability to routinely measure adducts in the 1 per 10 8 nucleotide range from a few micrograms of DNA is compelling, even if structural information is limited.…”

Section: Introductionmentioning

confidence: 99%

DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine

Stornetta

Zimmermann

Cimino

et al. 2017

Chem. Res. Toxicol.

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Biomarker-driven drug selection plays a central role in cancer drug discovery and development, and in diagnostic strategies to improve the use of traditional chemotherapeutic drugs. DNA-modifying anticancer drugs are still used as first line medication, but drawbacks such as resistance and side effects remain an issue. Monitoring the formation and level of DNA modifications induced by anticancer drugs is a potential strategy for stratifying patients and predicting drug efficacy. In this perspective, preclinical and clinical data concerning the relationship between drug-induced DNA adducts and biological response for platinum drugs and combination therapies, nitrogen mustards and half-mustards, hypoxia-activated drugs, reductase-activated drugs, and minor groove binding agents are presented and discussed. Aspects including measurement strategies, identification of adducts, and biological factors that influence the predictive relationship between DNA modification and biological response are addressed. A positive correlation between DNA adduct levels and response was observed for the majority of the studies, demonstrating the high potential of using DNA adducts from anticancer drugs as mechanism-based biomarkers of susceptibility, especially as bioanalysis approaches with higher sensitivity and throughput emerge.

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Copper‐Related Cell Death and the Role of Copper in Head and Neck Squamous Cell Carcinoma and Therapeutic Strategies

Zhang,

Wu,

Wang

et al. 2024

Advanced Therapeutics

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As an essential mineral element for the human body, copper (Cu) is necessary for various physiological functions. Excess or deficiency of copper causes cytotoxicity and damages the body. Thus, strict regulatory mechanisms are required to maintain copper homeostasis. Copper correlates closely to many forms of cell death. A recent study found that copper‐dependent cell death, known as cuproptosis, is different from all other known forms of cell death. This discovery helps us further understand the role of copper in cytotoxicity. Copper dysregulation occurs in a variety of malignancies, including head and neck squamous cell carcinoma (HNSCC), which is the eighth most common malignancy worldwide. This may increase the risk of HNSCC from a population perspective. Further exploring molecular mechanisms of copper in HNSCC will contribute to provide new therapeutic opportunities. Here we review the physiological metabolism and functions of copper, as well as copper‐related cell death. We focus on the research advances of copper in HNSCC, including the epidemiology and molecular mechanisms, as well as therapeutic strategies targeting copper homeostasis.This article is protected by copyright. All rights reserved

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Mechanistic basis of a combination d-penicillamine and platinum drugs synergistically inhibits tumor growth in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

Cited by 35 publications

References 33 publications

Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine

Copper‐Related Cell Death and the Role of Copper in Head and Neck Squamous Cell Carcinoma and Therapeutic Strategies

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