Evidence map›Paper›PMID 28904007›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2017

Synthetic Analogs of Curcumin Modulate the Function of Multidrug Resistance-Linked ATP-Binding Cassette Transporter ABCG2.

Megumi Murakami, Shinobu Ohnuma, Michihiro Fukuda, Eduardo E Chufan, Katsuyoshi Kudoh, Keigo Kanehara, Norihiko Sugisawa, Masaharu Ishida, Takeshi Naitoh, Hiroyuki Shibata and 3 more

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In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.0field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 44 citations in OpenAlex.

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  3. Novel cyclic CCancer cell international · 2025
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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

13 authors at 1 institution in 2 countries.

Megumi MurakamiDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Shinobu OhnumaDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.) sohnuma@surg1.med.tohoku.ac.jp.
Michihiro FukudaDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Eduardo E ChufanDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Katsuyoshi KudohDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Keigo KaneharaDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Norihiko SugisawaDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Masaharu IshidaDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Takeshi NaitohDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Hiroyuki ShibataDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Yoshiharu IwabuchiDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
Suresh V AmbudkarDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).ORCID 0000-0002-2639-4955
Michiaki UnnoDepartment of Surgery, Graduate School of Medicine (M.M., S.O., K.Ku., K.Ka., N.S., M.I., T.N., M.U.), and Laboratory of Synthetic Chemistry, Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences (M.F., Y.I.), Tohoku University, Sendai, Japan; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (E.E.C., S.V.A.); and Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan (H.S.).
National Institutes of Health · US

Funding

Biochemical Analysis of Multidrug Resistance-linked Transport ProteinsZIABC010030 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI AMBUDKAR, SURESH · 2009 to 2025
$21.6M
6 · The paper itself

Abstract

Multidrug resistance (MDR) caused by the overexpression of ATP-binding cassette (ABC) transporters in cancer cells is a major obstacle in cancer chemotherapy. Previous studies have shown that curcumin, a natural product and a dietary constituent of turmeric, inhibits the function of MDR-related ABC transporters, including ABCB1, ABCC1, and especially ABCG2. However, the limited bioavailability of curcumin prevents its use for modulation of the function of these transporters in the clinical setting. In this study, we investigated the effects of 24 synthetic curcumin analogs with increased bioavailability on the transport function of ABCG2. The screening of the 24 synthetic analogs by means of flow cytometry revealed that four of the curcumin analogs (GO-Y030, GO-Y078, GO-Y168, and GO-Y172) significantly inhibited the efflux of the ABCG2 substrates, mitoxantrone and pheophorbide A, from ABCG2-overexpressing K562/breast cancer resistance protein (BCRP) cells. Biochemical analyses showed that GO-Y030, GO-Y078, and GO-Y172 stimulated the ATPase activity of ABCG2 at nanomolar concentrations and inhibited the photolabeling of ABCG2 with iodoarylazidoprazosin, suggesting that these analogs interact with the substrate-binding sites of ABCG2. In addition, when used in cytotoxicity assays, GO-Y030 and GO-Y078 were found to improve the sensitivity of the anticancer drug, SN-38, in K562/BCRP cells. Taken together, these results suggest that nontoxic synthetic curcumin analogs with increased bioavailability, especially GO-Y030 and GO-Y078, inhibit the function of ABCG2 by directly interacting at the substrate-binding site. These synthetic curcumin analogs could therefore be developed as potent modulators to overcome ABCG2-mediated MDR in cancer cells.

Indexed as

Antineoplastic AgentsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2AzidesBenzene DerivativesBiological AvailabilityBiological TransportCamptothecinCell Line, TumorCurcuminDrug Resistance, NeoplasmDrug SynergismFlow CytometryHumansIrinotecanKetones1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-oneABCB1 protein, humanABCG2 protein, humanAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2AzidesazidoprazosinBenzene DerivativesCamptothecinCurcuminGO-Y030 compoundGO-Y078IrinotecanKetonesMitoxantroneNeoplasm ProteinsPrazosin

Identifiers

PMID28904007
PMCPMC5637816
OpenAlexW2755295552

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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.