The modulation of ABC transporter-mediated multidrug resistance in cancer: A review of the past decade

Kathawala, Rishil J.; Gupta, Pranav; Ashby, Charles R.; Chen, Zhe‐Sheng

doi:10.1016/j.drup.2014.11.002

Cited by 633 publications

(520 citation statements)

References 210 publications

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“…The use of combination therapies aims to overcome resistance to single agents. However, drug resistant cancer cells develop many times acquiring decreased sensitivity to a broad spectrum of structurally and functionally different drugs, a phenomenon early recognized and termed MDR (33). During tumor progression, epithelial cells lose polarity and acquire characteristics of mesenchymal cells including the capacity to invade surrounding tissues.…”

Section: Discussionmentioning

confidence: 99%

miR-106b~25 cluster regulates multidrug resistance in an ABC transporter-independent manner via downregulation of EP300

Asaduzzaman

et al. 2015

Oncology Reports

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Abstract. MicroRNA (miR)-106b~25 cluster regulates bypass of doxorubicin and γ-radiation induced senescence by downregulation of the E-cadherin transcriptional activator EP300. We asked whether upregulation of miR-106~25 cluster generates cells with a truly multidrug resistant (MDR) phenotype and whether this is due to upregulation of the ATP-binding cassette (ABC) transporter P-glycoprotein. We used minimally transformed mammary epithelial breast cancer cells (MTMECs) in which the miR-106b~25 cluster was experimentally upregulated by lentiviral transfection or in which hairpins targeting either EP300 or E-cadherin mRNAs have been expressed with lentiviruses. We find that overexpression of miR-106b~25 cluster led to the generation of MDR MTMECs (resistant to etoposide, colchicine and paclitaxel). Paclitaxel resistance was also studied after experimental downregulation of EP300 or E-cadherin. However none of these cells overexpressed P-glycoprotein or where able to efflux a fluorescent derivative of paclitaxel, making this phenotype drug-transporter independent. Paclitaxel treatment in MTMECs led to an increase in early apoptotic cells (Annexin V-positive), activation of caspase-9 and increase in the proportion of cells at the G2/M phase of the cell cycle. However, MTMEC overexpressing miR-106b~25 cluster, or with EP300 or E-cadherin downregulated, showed less activation of apoptosis, caspase-9 and caspase-3/-7 activities. Thus, miR-106b~25 cluster controls transporter-independent MDR by apoptosis evasion via downregulation of EP300.

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Section: Discussionmentioning

confidence: 99%

miR-106b~25 cluster regulates multidrug resistance in an ABC transporter-independent manner via downregulation of EP300

Asaduzzaman

et al. 2015

Oncology Reports

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“…It has been observed that one of the most common mechanisms of cancer MDR is the over-expression of the efflux pumps 29 , which are membrane proteins that can recognise and extrude out of the cells toxic agents such as the anticancer drugs 29,30 . In this context, different studies 6,7,[14][15][16][31][32][33] pointed out that selenocompounds can enhance the activity of the drugs used in cancer chemotherapy in a synergic way if they are applied together.…”

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confidence: 99%

Selenoesters and selenoanhydrides as novel multidrug resistance reversing agents: A confirmation study in a colon cancer MDR cell line

Gajdács

Spengler

Sanmartín

et al. 2017

Bioorganic & Medicinal Chemistry Letters

103

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“…Marine natural products are one of the most interesting targets for global drug discovery since they not only possess structural and chemical uniqueness but also represent novel scaffolds for drug development [34]. Marine natural products have also been studied and tested alongside with synthetic compounds as ABC transporter inhibitors [29,[35][36][37][38]. The development of anticancer drugs from marine compounds is one of the most promising approaches in drug discovery with therapeutic agents in clinical practice, such as the anticancer trabectedin [37].…”

Section: Introductionmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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The modulation of ABC transporter-mediated multidrug resistance in cancer: A review of the past decade

Cited by 633 publications

References 210 publications

miR-106b~25 cluster regulates multidrug resistance in an ABC transporter-independent manner via downregulation of EP300

miR-106b~25 cluster regulates multidrug resistance in an ABC transporter-independent manner via downregulation of EP300

Selenoesters and selenoanhydrides as novel multidrug resistance reversing agents: A confirmation study in a colon cancer MDR cell line

Marine Natural Products as Models to Circumvent Multidrug Resistance

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