Evidence map›Paper›PMID 24737138›Full record

ArticleMolecular pharmacology2014

Antileukemic activity and mechanism of drug resistance to the marine Salinispora tropica proteasome inhibitor salinosporamide A (Marizomib).

Denise Niewerth, Gerrit Jansen, Lesley F V Riethoff, Johan van Meerloo, Andrew J Kale, Bradley S Moore, Yehuda G Assaraf, Janet L Anderl, Sonja Zweegman, Gertjan J L Kaspers and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 45 citations in OpenAlex.

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  19. Natural compounds for pediatric cancer treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2016
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 3 countries.

Denise NiewerthDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Gerrit JansenDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Lesley F V RiethoffDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Johan van MeerlooDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Andrew J KaleDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Bradley S MooreDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Yehuda G AssarafDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Janet L AnderlDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Sonja ZweegmanDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Gertjan J L KaspersDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.).
Jacqueline CloosDepartment of Pediatric Oncology/Hematology (D.N., L.F.V.R., J.v.M., G.J.L.K., J.C.), Department of Rheumatology (G.J.), and Department of Hematology (J.v.M., S.Z., J.C.), VU University Medical Center, Amsterdam, The Netherlands; Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, California (A.J.K., B.S.M.); The Fred Wyszkowski Cancer Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel (Y.G.A.); and Research Department, Onyx Pharmaceuticals Inc., South San Francisco, California (J.L.A.) j.cloos@vumc.nl.
Scripps Institution of Oceanography · USTechnion – Israel Institute of Technology · IL

Funding

Salinosporamide Biosynthesis and EngineeringR01CA127622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MOORE, BRADLEY S · 2007 to 2016
$2.8M
NCI NIH HHS R01 CA127622NCI NIH HHS R01-CA127622
6 · The paper itself

Abstract

Salinosporamide A (NPI-0052, marizomib) is a naturally occurring proteasome inhibitor derived from the marine actinobacterium Salinispora tropica, and represents a promising clinical agent in the treatment of hematologic malignancies. Recently, these actinobacteria were shown to harbor self-resistance properties to salinosporamide A by expressing redundant catalytically active mutants of the 20S proteasome β-subunit, reminiscent of PSMB5 mutations identified in cancer cells with acquired resistance to the founding proteasome inhibitor bortezomib (BTZ). Here, we assessed the growth inhibitory potential of salinosporamide A in human acute lymphocytic leukemia CCRF-CEM cells, and its 10-fold (CEM/BTZ7) and 123-fold (CEM/BTZ200) bortezomib-resistant sublines harboring PSMB5 mutations. Parental cells displayed sensitivity to salinosporamide A (IC50 = 5.1 nM), whereas their bortezomib-resistant sublines were 9- and 17-fold cross-resistant to salinosporamide A, respectively. Notably, combination experiments of salinosporamide A and bortezomib showed synergistic activity in CEM/BTZ200 cells. CEM cells gradually exposed to 20 nM salinosporamide A (CEM/S20) displayed stable 5-fold acquired resistance to salinosporamide A and were 3-fold cross-resistant to bortezomib. Consistent with the acquisition of a PSMB5 point mutation (M45V) in CEM/S20 cells, salinosporamide A displayed a markedly impaired capacity to inhibit β5-associated catalytic activity. Last, compared with parental CEM cells, CEM/S20 cells exhibited up to 2.5-fold upregulation of constitutive proteasome subunits, while retaining unaltered immunoproteasome subunit expression. In conclusion, salinosporamide A displayed potent antileukemic activity against bortezomib-resistant leukemia cells. β-Subunit point mutations as a common feature of acquired resistance to salinosporamide A and bortezomib in hematologic cells and S. tropica suggest an evolutionarily conserved mechanism of resistance to proteasome inhibitors.

Indexed as

ActinobacteriaBoronic AcidsBortezomibCatalysisCell Line, TumorDrug Resistance, NeoplasmHumansLactonesLeukemiaMutationProteasome Endopeptidase ComplexProteasome InhibitorsPyrazinesPyrrolesUp-RegulationBoronic AcidsBortezomibLactonesmarizomibProteasome Endopeptidase ComplexProteasome InhibitorsPSMB5 protein, humanPyrazinesPyrroles

Identifiers

PMID24737138
PMCPMC4054006
OpenAlexW2168172745

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.