Celecoxib sensitizes imatinib-resistant K562 cells to imatinib by inhibiting MRP1–5, ABCA2 and ABCG2 transporters via Wnt and Ras signaling pathways

Dharmapuri, Gangappa; Doneti, Ravinder; Philip, Gundala Harold; Kalle, Arunasree M.

doi:10.1016/j.leukres.2015.02.013

Cited by 44 publications

(32 citation statements)

References 20 publications

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“…showed that a combination of LY294002 with gefitinib could downregulate BCRP expression, which gives a hint that downregulation of ABC transporters mediated by kinase inhibitors is one mechanism of the sensitization of tumor cells that overexpress these efflux pumps. This is in agreement with the stated findings that other TKIs also reduced MRP1 expression, such as imatinib, lapatinib, sunitinib, SB203580 (Figure ), and selumetinib (AZD6244; Figure ) …”

Section: Pharmacological and Experimental Drugs And Synthetic Analogssupporting

confidence: 92%

“…But it has to be stated that the compounds also affected P‐gp‐mediated calcein AM transport as well as ATPase activity, and must be considered as unselective in this regard. Interestingly, a combination of imatinib (10 μM) with celecoxib (10 μM) was found to downregulate MRP1 expression in IR‐K562 cells . The downregulation of MRP1 by celecoxib has already been stated above …”

Section: Pharmacological and Experimental Drugs And Synthetic Analogssupporting

confidence: 57%

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Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Stefan

Wiese

2018

Medicinal Research Reviews

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Multidrug resistance-associated protein 1 (MRP1, ABCC1) is an ATP-binding cassette (ABC) transport protein. This efflux pump uses the energy of ATP hydrolysis to export structurally diverse antineoplastic agents in human cancers. The upregulation of MRP1 (either inherent or acquired) is one major reason for the occurrence of the phenomenon called multidrug resistance (MDR). MDR is characterized by a reduced outcome of chemotherapy due to the active intracellular clearance of cytostatic drugs below the necessary effect concentration. Much effort has been made to overcome MDR, which implied high-throughput screenings of already known pharmacological and natural compounds, modification of intrinsic substrates, as well as design and synthesis of new inhibitors. This review is meant not only to summarize the most recent results over the past 10 years, but also to highlight major achievements regarding reversal of MRP1-mediated MDR, from the time of its discovery until today. The focus lies on small-molecule compounds that feature either direct MRP1 inhibition/transport blockage, toxicity against MRP1-overexpressing cells, inhibition/modification of intracellular processes necessary for MRP1 function, or modification of MRP1-related metabolic and genomic mechanisms. Considering all aspects, this review might be useful to (re)consider possible strategies to overcome MRP1-mediated MDR. Furthermore, it may be the basis for developing new, even better, highly potent, less toxic, and selective (as well as broad-spectrum) MRP1 inhibitors that will enter clinical evaluations in different malignancies and finally conduce to overcome MDR in general.

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Section: Pharmacological and Experimental Drugs And Synthetic Analogssupporting

confidence: 92%

Section: Pharmacological and Experimental Drugs And Synthetic Analogssupporting

confidence: 57%

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Stefan

Wiese

2018

Medicinal Research Reviews

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“…MDR is often associated with overexpression of drug efflux transporters belonging to adenosine triphosphate (ATP)-dependent binding cassette (ABC) protein family (3). A large number of studies revealed that multidrug resistance 1 (MDR1), also known as P-glycoprotein or ABCB1, and multidrug resistance-associated protein 1 (MRP1), also known as ABCC1, which are ABC transporters and work as drug efflux pumps, play crucial roles in MDR of human CML (2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway

Chen

Xing

Wang

et al. 2016

International Journal of Oncology

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One of the major causes of failure in chemotherapy for patients with human chronic myelogenous leukemia (CML) is the acquisition of multidrug resistance (MDR). MDR is often associated with the overexpression of drug efflux transporters of the ATP-binding cassette (ABC) protein family. Timosaponin A-III (TAIII), a saponin isolated from the rhizome of Anemarrhena asphodeloides, has previously demonstrated the ability to suppress certain human tumor processes and the potential to be developed as an anticancer agent. Nevertheless, the ability of TAIII to reverse MDR has not yet been explored. In this study, the adriamycin (ADM) resistance reversal effect of TAIII in human CML K562/ADM cells and the underlying mechanism was investigated. The Cell Counting Kit-8 (CCK-8) assay showed that TAIII had a reversal effect on the drug resistance of K562/ADM cells. Flow cytometry assay showed increased intracellular accumulation of ADM after cells were pretreated with TAIII, and the changes in the accumulation of rhodamine-123 (Rho-123) and 5(6)-carboxyfluorescein diacetate (CFDA) dye in K562/ADM cells were determined to be similar to the changes of intracellular accumulation of ADM. After pretreatment of cells with TAIII, the decreasing expression of P-gp and MRP1 mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). Western blotting showed TAIII inhibiting P-gp and MRP1 expression depended on the PI3K/Akt signaling pathway by decreasing the activity of p-Akt. Moreover, wortmannin an inhibitor of PI3K/Akt signaling pathway has a strong inhibitory effect on the expression of p-Akt, P-gp and MRP1. Besides, the combined treatment with TAIII did not have an affect on wortmannin downregulation of p-Akt, P-gp and MRP1. Taken together, our findings demonstrate, for the first time, that TAIII induced MDR reversal through inhibition of P-gp and MRP1 expression and function with regained adriamycin sensitivity which might mainly correlate to the regulation of PI3K/Akt signaling pathway.

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“…Experiments have shown that SMAD4 inactivation promotes drug resistance in cancer (Zhang et al 2014; Raz et al 2014). ABCA2 is a member of ATP-binding cassette (ABC) transporters that transports many kinds of small molecules through membranes and is involved in drug resistance in leukemia cell lines (Dharmapuri et al 2015). …”

Section: Discussionmentioning

confidence: 99%

Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells

Miao

Peng

et al. 2016

SpringerPlus

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Docetaxel has been the standard first-line therapy in metastatic castration resistant prostate cancer. The survival benefit is, however, limited by either primary or acquired resistance. In this study, Du145 prostate cancer cells were converted to docetaxel-resistant cells Du145-R and Du145-RB by in vitro culturing. Next generation RNAseq was employed to analyze these cell lines. Forty-two genes were identified to have acquired mutations after the resistance development, of which thirty-four were found to have mutations in published sequencing studies using prostate cancer samples from patients. Fourteen novel and 2 previously known fusion genes were inferred from the RNA-seq data, and 13 of these were validated by RT-PCR and/or re-sequencing. Four in-frame fusion transcripts could be transcribed into fusion proteins in stably transfected HEK293 cells, including MYH9-EIF3D and LDLR-RPL31P11, which were specific identified or up-regulated in the docetaxel resistant DU145 cells. A panel of 615 gene transcripts was identified to have significantly changed expression profile in the docetaxel resistant cells. These transcriptional changes have potential for further study as predictive biomarkers and as targets of docetaxel treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3543-0) contains supplementary material, which is available to authorized users.

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Celecoxib sensitizes imatinib-resistant K562 cells to imatinib by inhibiting MRP1–5, ABCA2 and ABCG2 transporters via Wnt and Ras signaling pathways

Cited by 44 publications

References 20 publications

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances

Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway

Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells

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