Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles

Myint, Khine; Li, Yan; Paxton, James W.; McKeage, Mark J.

doi:10.1371/journal.pone.0130727

Cited by 32 publications

(18 citation statements)

References 45 publications

(52 reference statements)

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“…ATP7A/7B, which belongs to P-type ATPases, is responsible for copper homeostasis (Gupta and Lutsenko, 2009). After getting into the cells, platinum may bind to the CXXC motifs of ATP7A/ B (Safaei et al, 2012), then the complex translocates into a vesicle Yonezawa et al, 2006); (Taniguchi et al, 1996;Borst et al, 2000;Samimi et al, 2004;Yokoo et al, 2007;Safaei et al, 2008;Blair et al, 2009;Beretta et al, 2010;Burger et al, 2010;Myint et al, 2015) Cisplatin…”

Section: Atp7a and Atp7bmentioning

confidence: 99%

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

et al. 2020

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Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

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Section: Atp7a and Atp7bmentioning

confidence: 99%

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

et al. 2020

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“…The level of ATP-binding cassette sub-family G member 2 (ABCG2) mRNA was increased in HCT116/DocR cells, but declined in HT29/DocR and HT29/OxR cells. The multidrug resistance-associated protein 2 (mRP2), which was reported to be involved in the response to oxaliplatin (30), was increased in HT29/OxR cells but decreased in HCT116/DocR cells. The level of the organic anion transporting polypeptide 2B1 (OATP2B1), which contribution to docetaxel uptake and clearance is not well established (31), was evaluated.…”

Section: Drug Resistance and Expression Of Chemo-resistance-related Mmentioning

confidence: 99%

Acquisition of anticancer drug resistance is partially associated with cancer stemness in human colon cancer cells

Khoury

Corcos

Durand

et al. 2016

International Journal of Oncology

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Colorectal cancer (CRC) is one of the most aggressive cancers worldwide. Several anticancer agents are available to treat CRC, but eventually cancer relapse occurs. One major cause of chemotherapy failure is the emergence of drug-resistant tumor cells, suspected to originate from the stem cell compartment. The aim of this study was to ask whether drug resistance was associated with the acquisition of stem cell-like properties. We isolated drug-resistant derivatives of two human CRC cell lines, HT29 and HCT116, using two anticancer drugs with distinct modes of action, oxaliplatin and docetaxel. HT29 cells resistant to oxaliplatin and both HT29 and HCT116 cells resistant to docetaxel were characterized for their expression of genes potentially involved in drug resistance, cell growth and cell division, and by surveying stem cell-like phenotypic traits, including marker genes, the ability to repair cell-wound and to form colonospheres. Among the genes involved in platinum or taxane resistance (MDR1, ABCG2, MRP2 or ATP7B), MDR1 was uniquely overexpressed in all the resistant cells. An increase in the cyclin-dependent kinase inhibitor p21, in cyclin D1 and in CD26, CD166 cancer stem cell markers, was noted in the resistant cells, together with a higher ability to form larger and more abundant colonospheres. However, many phenotypic traits were selectively altered in either HT29- or in HCT116-resistant cells. Expression of EPHB2, ITGβ-1 or Myc was specifically increased in the HT29-resistant cells, whereas only HCT116-resistant cells efficiently repaired cell- wounds. Taken together, our results show that human CRC cells selected for their resistance to anticancer drugs displayed a few stem cell characteristics, a small fraction of which was shared between cell lines. The occurrence of marked phenotypic differences between HT29- and HCT116-drug resistant cells indicates that the acquired resistance depends mostly on the parental cell characteristics, rather than on the drug type used.

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“…Multiple mechanisms participate in DDP resistance, including increased drug efflux, drug inactivation, enhanced DNA damage repair, active survival signaling pathway and evasion of apoptosis [ 2 ]. Recently, the relevance of metabolic reprogramming to drug resistance received much attention [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer

Qian

et al. 2017

Oncotarget

106

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Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance.

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Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles

Cited by 32 publications

References 45 publications

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

Acquisition of anticancer drug resistance is partially associated with cancer stemness in human colon cancer cells

Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer

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