The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I

Kawatani, Masahito; Okumura, Hideo; Honda, Kaori; Kanoh, Naoki; Muroi, Makoto; Dohmae, Naoshi; Miki, Takami; Kitagawa, M.; Futamura, Yushi; Imoto, Masaya; Osada, Hiroyuki

doi:10.1073/pnas.0712239105

Cited by 125 publications

(107 citation statements)

References 44 publications

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“…It is also involved in the regulation of transcriptional activity of NF-kappa-B induced by TNF. Interstingly, it appears to be required for normal osteoclastogenesis and therefore involved in the complex mechanism of bone metastasis [84]. In our tumor tissue LGUL showed a fold increase of about 2x with respect to the non tumoral tissues.…”

Section: Lactoylglutathione Lyase Lgul (Glo1)mentioning

confidence: 49%

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Pucci‐Minafra¹,

Cara²,

Musso³

et al. 2017

Preprint

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Abstract:The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing postsurgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

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Section: Lactoylglutathione Lyase Lgul (Glo1)mentioning

confidence: 49%

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Pucci‐Minafra¹,

Cara²,

Musso³

et al. 2017

Preprint

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“…Binding Assay Using Luteolin-conjugated Beads-Luteolinconjugated agarose beads and control beads were kindly provided by RIKEN NPDepo (16). HepG2 cells were treated with 50 M luteolin or vehicle for 3 h, harvested and washed twice with PBS, and then resuspended in binding buffer (10 mM TrisHCl (pH 7.6), 50 mM KCl, 5 mM MgCl 2 , 1 mM EDTA, and a protease inhibitor mixture).…”

Section: Methodsmentioning

confidence: 99%

Identification of the Flavonoid Luteolin as a Repressor of the Transcription Factor Hepatocyte Nuclear Factor 4α

Inoue

Choi

et al. 2015

Journal of Biological Chemistry

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Background: Flavonoids are naturally occurring compounds that can regulate certain transcription factors. Results: We identified the flavonoid luteolin as a repressor of HNF4␣ and revealed that dietary luteolin improves high-fat diet-induced metabolic disorder in mice. Conclusion: HNF4␣ is a target of luteolin. Significance: Modulation of HNF4␣ activity through luteolin may be of therapeutic value in atherosclerotic disease.

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“…The Glo-I inhibitors, BBGC, COTC and methylgerfelin, were synthesized and purified as previously described. [26][27][28] The K562 cell line was obtained from the American Type Culture Collection (Manassas, VA, USA). The other CML-derived cell lines (KCL22, BV173 and MYL) were kindly provided by Dr Tadashi Nagai (Jichi Medical School, Tochigi, Japan), Dr Oliver G Ottmann (Frankfurt University, Frankfurt, Germany) and Dr Hideo Tanaka (Hiroshima University, Hiroshima, Japan), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…27 Recently, methyl-gerfelin (Supplementary Figure 7a) was also identified as a Glo-I inhibitor. 28 Although HA-CML cells were resistant to the cytotoxic effects of Abl TKIs and alkylating agents (Figures 2d and e, Table 1), BBGC, COTC and methyl-gerfelin were more strongly cytotoxic in K562/HA and KCL22/HA cells than in the parental cell lines (Figures 5a-d, Supplementary Figures 7b and c).…”

mentioning

confidence: 98%

Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in a hypoxic environment

et al. 2010

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Abl tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are ineffective against Bcr-Abl þ leukemic stem cells. Thus, the identification of novel agents that are effective in eradicating quiescent Bcr-Abl þ stem cells is needed to cure leukemias caused by Bcr-Abl þ cells. Human Bcr-Abl þ cells engrafted in the bone marrow of immunodeficient mice survive under severe hypoxia. We generated two hypoxia-adapted (HA)-Bcr-Abl þ sublines by selection in long-term hypoxic cultures (1.0% O 2 ). Interestingly, HA-Bcr-Abl þ cells exhibited stem cell-like characteristics, including more cells in a dormant, increase of side population fraction, higher b-catenin expression, resistance to Abl TKIs, and a higher transplantation efficiency. Compared with the respective parental cells, HA-Bcr-Abl þ cells had higher levels of protein and higher enzyme activity of glyoxalase-I (Glo-I), an enzyme that detoxifies methylglyoxal, a cytotoxic by-product of glycolysis. In contrast to Abl TKIs, Glo-I inhibitors were much more effective in killing HA-Bcr-Abl þ cells both in vitro and in vivo. These findings indicate that Glo-I is a novel molecular target for treatment of Bcr-Abl þ leukemias, and, in particular, Abl TKI-resistant quiescent Bcr-Abl þ leukemic cells that have acquired stem-like characteristics in the process of adapting to a hypoxic environment.

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The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I

Cited by 125 publications

References 44 publications

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Identification of the Flavonoid Luteolin as a Repressor of the Transcription Factor Hepatocyte Nuclear Factor 4α

Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in a hypoxic environment

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