ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine

Juan-Carlos, Pérez-De Marcos; Perla-Lidia, Pérez-Pineda; Stephanie-Talia, Méndez-Morales; Mónica-Griselda, Arellano-Mendoza; Torres‐Espíndola, Luz María

doi:10.1007/s11033-021-06155-w

Cited by 50 publications

(54 citation statements)

References 82 publications

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“…In order to investigate whether the nano-motion sensor could be used to identify cancer cells which are resistant to chemotherapy, we employed an in vitro MDR model system that comprises three different sensitive human cancer cell lines and their MDR counterparts. P-gp that is overexpressed in tested MDR cancer cell lines is a member of the ABC transporter family which reduces intracellular accumulation of anticancer drugs by increasing drug efflux, thus suppressing the interaction between the drug and its intracellular target molecule [ 20 ]. P-gp can bind a wide variety of hydrophobic drugs including DOX and PTX [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

et al. 2021

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Background and Objectives: Optimization of chemotherapy is crucial for cancer patients. Timely and costly efficient treatments are emerging due to the increasing incidence of cancer worldwide. Here, we present a methodology of nano-motion analysis that could be developed to serve as a screening tool able to determine the best chemotherapy option for a particular patient within hours. Materials and Methods: Three different human cancer cell lines and their multidrug resistant (MDR) counterparts were analyzed with an atomic force microscope (AFM) using tipless cantilevers to adhere the cells and monitor their nano-motions. Results: The cells exposed to doxorubicin (DOX) differentially responded due to their sensitivity to this chemotherapeutic. The death of sensitive cells corresponding to the drop in signal variance occurred in less than 2 h after DOX application, while MDR cells continued to move, even showing an increase in signal variance. Conclusions: Nano-motion sensing can be developed as a screening tool that will allow simple, inexpensive and quick testing of different chemotherapeutics for each cancer patient. Further investigations on patient-derived tumor cells should confirm the method’s applicability.

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Section: Resultsmentioning

confidence: 99%

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

et al. 2021

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“…MDR is one of the inevitable challenges in cancer treatment, especially in conventional chemotherapy and targeted therapy. When cancer cells develop MDR phenotype, it becomes insensitive to a broad range of anticancer drugs, which may lead to treatment failure ( Juan-Carlos et al, 2021 ). Importantly, overexpression of ABCG2 transporter is characterized as a major mechanism that regulates MDR in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of ABCG2 Confers Resistance to MLN7243, a Ubiquitin-Activating Enzyme (UAE) Inhibitor

Yang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Overexpression of ATP-binding cassette transporter superfamily G member 2 (ABCG2), is known as a major mechanism mediating multidrug resistance (MDR) in cancer cells. MLN7243 is a small-molecule ubiquitin activating enzyme inhibitor currently under clinical investigation. The aim of the current study is to determine if MLN7243 is a substrate of MDR-related ABCG2 transporter. Our results showed that cancer cells overexpressing ABCG2 transporter were resistant to MLN7243 compared to the parental cells, while knockout of ABCG2 gene or pharmacological inhibition of ABCG2 efflux function completely reversed the drug resistance. Unexpectedly, the endogenous low expression of ABCG2 is sufficient to confer cancer cells resistance to MLN7243. The ABCG2 ATPase assay and HPLC assay suggested that MLN7243 can significantly stimulate ABCG2 ATPase activity and be pumped out from ABCG2-overexpressing cells by ABCG2. The docking analysis also implied that MLN7243 binds to ABCG2 drug-binding pocket with optimal binding affinity. However, MLN7243 did not competitively inhibit the efflux of other ABCG2 substrate drugs, indicating it may not serve as an MDR reversal agent. In conclusion, our study provides direct in vitro evidence to show that MLN7243 is a potent ABCG2 substrate. If our results can be translated to humans, it suggests that combining MLN7243 with ABCG2 inhibitors may enhance the anticancer efficacy for patients with high tumor ABCG2 level.

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“…Although transporters were originally classified based on their functions, they are now classified according to the sequence homology of the isolated genes. Transporters are categorized into two superfamilies: ATP-binding cassette (ABC) transporters, which are involved in the efflux of substances, and solute carrier (SLC) transporters, which are mainly involved in the uptake of substances [ 1 , 2 ]. Transporters are involved in the transport of various physiological substances such as sugars, amino acids, and lipids, but some transporters are particularly relevant to pharmacokinetics and are thus recognized as drug transporters.…”

Section: Introductionmentioning

confidence: 99%

Overview of Drug Transporters in Human Placenta

Yamashita

Markert

2021

IJMS

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The transport of drugs across the placenta is a point of great importance in pharmacotherapy during pregnancy. However, the knowledge of drug transport in pregnancy is mostly based on experimental clinical data, and the underlying biological mechanisms are not fully understood. In this review, we summarize the current knowledge of drug transporters in the human placenta. We only refer to human data since the placenta demonstrates great diversity among species. In addition, we describe the experimental models that have been used in human placental transport studies and discuss their availability. A better understanding of placental drug transporters will be beneficial for the health of pregnant women who need drug treatment and their fetuses.

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ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine

Cited by 50 publications

References 82 publications

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

Nano-Motion Analysis for Rapid and Label Free Assessing of Cancer Cell Sensitivity to Chemotherapeutics

Overexpression of ABCG2 Confers Resistance to MLN7243, a Ubiquitin-Activating Enzyme (UAE) Inhibitor

Overview of Drug Transporters in Human Placenta

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