Reversal of anticancer drug resistance by COTC based on intracellular glutathione and glyoxalase I

Kamiya, Daisuke; Uchihata, Yuki; Ichikawa, Eiko; Kato, Kuniki; Umezawa, Kazuo

doi:10.1016/j.bmcl.2004.12.031

Cited by 28 publications

(12 citation statements)

References 16 publications

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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%

“…S-p-bromobenzyl glutathione cyclopentyl diester (BBGC) (Figure 3f) is a specific cell-permeable inhibitor of Glo-I, 26 and 2-crotonyloxymethyl-4,5,6-trihydroxycylohex-2-enone (COTC) (Figure 3g) is an inhibitor of Glo-I and glutathione. 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).…”

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confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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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“…Recently, it has been shown that GloI is involved also in resistance of human leukaemia cells to anti-tumour agent-induced apoptosis [21]. Furthermore, in apoptosis-resistant pancreatic adenocarcinoma AsPC-1 cells, inhibition of GloI increased chemotherapy-mediated apoptosis, reverting resistance of these cells to anti-tumour agents [22].…”

Section: Introductionmentioning

confidence: 99%

A possible regulatory role of 17β-estradiol and tamoxifen on glyoxalase I and glyoxalase II genes expression in MCF7 and BT20 human breast cancer cells

Rulli

Antognelli

Prezzi

et al. 2005

Breast Cancer Res Treat

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The glutathione-dependent glyoxalases system, composed of glyoxalase I (GloI) and glyoxalase II (GloII) enzymes, is involved in the detoxification of methylglyoxal, a by-product of cell metabolism. Aberrations in the expression of glyoxalase genes in several human cancers have been reported. Sometimes, these aberrations seem to differ depending on the organs and on the sensitivity of the tumours to estrogens, as we previously detected in the hormone-responsive breast cancer compared to the hormone-independent bladder cancer. To investigate a possible regulatory role of estrogens, as well as antiestrogens, on glyoxalases system, estrogen receptor (ER)-positive MCF7 and ER-negative BT20 human breast cancer cells were cultured in the presence of 17beta-estradiol (E2) and tamoxifen (TAM) performing two independent experiments. After a 24 h or 4 days treatment, we evaluated GloI and GloII mRNA levels, by Ribonuclease Protection Assay (RPA), enzymatic activities spectrophotometrically and cell proliferation by [3H]thymidine incorporation. We found that both steroid molecules affected glyoxalases gene expression and proliferation in a different manner in the cell lines. The modifications in mRNA levels were accompanied by parallel changes in the enzymatic activities. The possibility that modulation of glyoxalase genes by E2 and TAM are due to the presence of estrogen response elements (ERE) or cross-talk mechanisms by proteins of the estrogen signal transduction pathways are discussed. Knowledge regarding the regulation of glyoxalases by E2 and TAM may provide insights into the importance of this enzymes in human breast carcinomas in vivo.

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“…The general mechanism for anticancer activity of COTC is depicted in Scheme 19 [249][250][251][252][253].…”

Section: Mk-7067 Carbagalactopyranose Carbaglucopyranosementioning

confidence: 99%

Biosynthesis and Biological Activity of Carbasugars

Roscales

Plumet

2016

International Journal of Carbohydrate Chemistry

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The first synthesis of carbasugars, compounds in which the ring oxygen of a monosaccharide had been replaced by a methylene moiety, was described in 1966 by Professor G. E. McCasland's group. Seven years later, the first true natural carbasugar (5a-carba-R-D-galactopyranose) was isolated from a fermentation broth of Streptomyces sp. MA-4145. In the following decades, the chemistry and biology of carbasugars have been extensively studied. Most of these compounds show interesting biological properties, especially enzymatic inhibitory activities, and, in consequence, an important number of analogues have also been prepared in the search for improved biological activities. The aim of this review is to give coverage on the progress made in two important aspects of these compounds: the elucidation of their biosynthesis and the consideration of their biological properties, including the extensively studied carbapyranoses as well as the much less studied carbafuranoses.

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Reversal of anticancer drug resistance by COTC based on intracellular glutathione and glyoxalase I

Cited by 28 publications

References 16 publications

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

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

A possible regulatory role of 17β-estradiol and tamoxifen on glyoxalase I and glyoxalase II genes expression in MCF7 and BT20 human breast cancer cells

Biosynthesis and Biological Activity of Carbasugars

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