Identification of BMI1 Promoter Inhibitors from <i>Beaumontia murtonii</i> and <i>Eugenia operculata</i>

Kaneta, Yui; Arai, Midori A.; Ishikawa, Naoki; Toume, Kazufumi; Koyano, Takashi; Kowithayakorn, Thaworn; Chiba, Tetsuhiro; Iwama, Atsushi; Ishibashi, Masami

doi:10.1021/acs.jnatprod.7b00138

Cited by 12 publications

(16 citation statements)

References 29 publications

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“…A major known compound, (+)-ursolic acid (1) , 18 was purified from this extraction process, and it was found to exhibit cytotoxic and NF-κB inhibitory activities. Following this result, the CHCl3 extract was subjected to chromatographic separation guided by HT-29 cells and NF-κB inhibition, and 18 known compounds, (+)-fouquierol (2) , 19 (+)-melaleucic acid 28-methyl ester (3) , 20 (+)-melaleucic acid (4) , 21 (+)-alphitolic acid (5) , 22 (+)-cylicodiscic acid (6) , 23 (+)-3- O −β- trans-p −coumaroylalphitolic acid (7) , 24 3,4-methylenedioxy-3’- O −methylellagic acid (S1) , 25 3,4-methylenedioxy-3’,4’,5’-tri- O −methylellagic acid (S2) , 26 3,3’,4’-tri- O −methylellagic acid (S3) , 27 sideroxylin (S4) , 28 (+)-2,3-dihydrosideroxylin (S5) , 29 (+)-3-hydroxy-6,10- seco −muurol-1-ene-6,10-dione (S6) , 30 (+)-dehydrovomifoliol (S7) , 31 (+)-3-oxo-α-ionol (S8) , 32 (+)-annuionone D (S9) , 33 (+)-vomifoliol (S10) , 34 (−)-loliolide (S11) , 35 and syringaldehyde (S12) , 36 were isolated from S. corticosum .…”

Section: Resultsmentioning

confidence: 99%

“…S1–S7 and S14–S25 and Tables S1–S6, supplementary data). The NMR spectroscopic data for (+)-melaleucic acid 28-methyl ester (3) were measured in a deuterated solvent different from that used previously, 20 owing to its limited solubility in CDCl 3 , and these data were assigned completely in the present study (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“… c 1 H NMR spectroscopic data (δ) measured in CDCl 3 at 400.13 MHz and referenced to the solvent residual peak at δ 7.26. 40 d 13 C NMR spectroscopic data (δ) measured in acetone- d 6 (different from that used in literature 20 ) at 100.61 MHz and referenced to the solvent residual peak at δ 29.84 40 e 1 H NMR spectroscopic data (δ) measured in acetone- d 6 (different from that used in hat used in literature 20 ) at 400.13 MHz and referenced to the solvent residual peak at δ 2.05 40 …”

Section: Figmentioning

confidence: 99%

“… e 1 H NMR spectroscopic data (δ) measured in acetone- d 6 (different from that used in hat used in literature 20 ) at 400.13 MHz and referenced to the solvent residual peak at δ 2.05 40 …”

Section: Figmentioning

confidence: 99%

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Cytotoxic and NF-κB and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives

Ren

Anaya-Eugenio

Czarnecki

et al. 2018

Bioorganic & Medicinal Chemistry

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Syzygium is a large genus of flowering plants, with several species, including the clove tree, used as important resources in the food and pharmaceutical industries. In our continuing search for anticancer agents from higher plants, a chloroform extract of the leaves and twigs of Syzygium corticosum collected in Vietnam was found to be active toward the HT-29 human colon cancer cell line. Separation of this extract guided by HT-29 cells and nuclear factor-kappa B (NF-κB) inhibition yielded 19 known natural products, including seven triterpenoids, three ellagic acid derivatives, two methylated flavonoids, a cyclohexanone, four megastigmanes, a small lactone, and an aromatic aldehyde. The full stereochemistry of (+)-fouquierol (2) was defined for the first time. Biological investigations showed that (+)-ursolic acid (1) is the major cytotoxic component of S. corticosum, which exhibited also potent activities in the NF-κB and mitochondrial transmembrane potential (MTP) inhibition assays conducted, with IC values of 31 nM and 3.5 µM, respectively. Several analogues of (+)-ursolic acid (1) were synthesized, and a preliminary structure-activity relationship (SAR) study indicated that the C-3 hydroxy and C-28 carboxylic acid groups and 19,20-dimethyl substitution are all essential in the mediation of the bioactivities observed for this triterpenoid.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

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Cytotoxic and NF-κB and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives

Ren

Anaya-Eugenio

Czarnecki

et al. 2018

Bioorganic & Medicinal Chemistry

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“…The most active compound, wallichoside, was shown to decrease Bmi1 protein levels in colon carcinoma cells and reduced selfrenewing capacity of human hepatocellular carcinoma cells. 76 However, further in vivo studies in human-mouse xenograft models are warranted to generate better understanding of the compound's therapeutic value. Additionally, molecules targeting Bmi1 transcript have been shown to hold a promising therapeutic potential in reducing oncogenic potential of prostate CSCs 77 and hepatocellular carcinoma.…”

Section: However In the Absence Of Bmi1 P16-mediated Inhibition Of mentioning

confidence: 99%

Bmi1 – A Path to Targeting Cancer Stem Cells

Bakhshinyan¹,

Adile²,

Venugopal³

et al. 2017

European Oncology &Amp; Haematology

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T he Polycomb group (PcG) genes encode for proteins comprising two multiprotein complexes, Polycomb repressive complex 1 (PRC1) and Polycomb repressive complex 2 (PRC2). Although the initial discovery of PcG genes was made in Drosophila, as transcriptional repressors of homeotic (HOX) genes. Polycomb repressive complexes have been since implicated in regulating a wide range of cellular processes, including differentiation and self-renewal in normal and cancer stem cells. Bmi1, a subunit of PRC1, has been long implicated in driving self-renewal, the key property of stem cells. Subsequent studies showing upregulation of Bmi1 in several cancers correlated with increased aggressiveness, radioresistance and metastatic potential, provided rationale for development of targeted therapies against Bmi1. Although Bmi1 activity can be reduced through transcriptional, post-transcriptional and post-translational regulation, to date, the most promising approach has been through small molecule inhibitors targeting Bmi1 activity. The post-translational targeting of Bmi1 in colorectal carcinoma, lung adenocarcinoma, multiple myeloma and medulloblastoma have led to significant reduction of self-renewal capacity of cancer stem cells, leading to slower tumour progression and reduced extent of metastatic spread. Further value of Bmi1 targeting in cancer can be established through trials evaluating the combinatorial effect of Bmi1 inhibition with current 'gold standard' therapies. KeywordsPolycomb group (PcG) genes, Bmi1, Mel-18, cancer stem cells (CSCs), self-renewal Disclosure: David Bakhshinyan, Ashley A Adile, Chitra Venugopal and Sheila K Singh have nothing to disclose in relation to this article.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Compliance with Ethics:This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. 1 PRC2 initiates gene silencing through the activity of histone deacetylase (HDAC), and histone methyltransferases that can methylate lysine 9 and 27 residues on histone H3 and lysine 26 on histone H1.2-6 The stable gene repression is then maintained by PRC1 through recognition of tri-methylated H3K27 (H3K27me3).3 The canonical repression pathway is initiated through trimethylation of H3K27 on the promoter of target gene by PRC2 subunit EZH1 or its paralog EZH2.2-4 The H3K27me3 mark is readily recognised by PRC1 through chromatin binding ability of its subunit CBX. The repression is further maintained through ubiquitination of lysine 119 residue on histone H2A (H2AK119ub) by RING1, a subunit of PRC1, or chromatin condensation. [7][8][9] Promoters of the polycomb target genes have been generally characterised as CpG-rich DNA sequences that are lacking other epigenetic markers.10-14 However, several other models of context depen...

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