The Mitomycin C (MMC)-binding Protein from MMC-producing Microorganisms Protects from the Lethal Effect of Bleomycin: Crystallographic Analysis to Elucidate the Binding Mode of the Antibiotic to the Protein

Danshiitsoodol, Narandalai; Pinho, C.A. de; Matoba, Yasuyuki; Kumagai, Toru; Sugiyama, Masanori

doi:10.1016/j.jmb.2006.05.017

Cited by 43 publications

(34 citation statements)

References 27 publications

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“…It may be treated either by removal of the bladder or by radiation therapy and chemotherapy (25). MMC, anaziridine-containing natural product (26), is often applied as a chemotherapeutic agent for the treatment of bladder cancer (7)(8)(9)(10)(11). Numerous individuals with heart disease in China also take MMC (27,28).…”

Section: Discussionmentioning

confidence: 99%

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

Zhang

Chen²,

Dong³

et al. 2018

Oncol Lett

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Abstract. The occurrence of resistance to mitomycin C (MMC) often limits its clinical effectiveness. Combination therapy thus is employed to overcome this treatment resistance. The present study aimed to establish a novel J82 bladder cancer cell line so as to study the effect of inhibition of aquaporin 1 (AQP-1) on chemotherapy sensitivity of J82 bladder cancer cells. A novel J82 bladder cancer cell line whose expression of AQP-1 is inhibited was established through transfection of J82 cells with newly constructed recombinant plasmid. The resulting cell line was designated J82-short hairpin (sh)AQP1 and was subjected to further analyses together with J82 cell line. Reverse transcription-polymerase chain reaction was used to quantify the expression of AQP-1mRNA in the cells; cell viability was analyzed with MTT assay and apoptosis was measured by flow cytometry. The expression of cell proliferation and cell apoptosis-associated proteins, proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3, were detected by Western blot. A statistically significant decrease in the transcription and expression of AQP1 was observed in the J82-shAQP1 cells as compared with J82 cells. J82-shAQP1 cells treated by MMC, also had a lower cell viability than J82 cells treated by MMC and showed enhanced apoptosis. Western blot analysis revealed J82-shAQP1 cells treated by MMC had less expression of PCNA, lower bcl-2/Bax ratio and more expression of caspase-3 as compared with the J82 cells treated by MMC. Selective inhibition of AQP-1 enhanced MMC chemotherapy sensitivity of J82 bladder cancer cells, suggesting combination of AQP-1 inhibition with MMC treatment as a promising treatment strategy to overcome bladder cancer treatment resistance.

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Section: Discussionmentioning

confidence: 99%

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

Zhang

Chen²,

Dong³

et al. 2018

Oncol Lett

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“…4−12 Copper is also known to activate bleomycin and attack DNA in a similar way to (but less much efficiently than) iron-bleomycin. 13 Structural data on Cu-bleomycin is available showing that copper binds in a very similar way to iron, 14,15 with some indication for partial deligation of the amide nitrogen from Cu(I) under certain conditions, supported also by molecular dynamics calculations. 17 Nevertheless, essentially nothing is known on possible reactive intermediates during dioxygen activation by Cu-bleomycin.…”

Section: Introductionmentioning

confidence: 89%

“…One important feature is the fact that dioxygen binding and reduction at the bleomycin-bound copper appears to entail cleavage of at least one copper-nitrogen bonds, as expected since these intermediates would imply coordination numbers distinctly higher than those normally preferred by copper -even though prior to dioxygen binding according to experimental data Cu(II) binds to bleomycin in a manner essentially identical to iron or cobalt, in pentacoordinated manner. 14,15 Thus, two coppernitrogen bonds are broken in the Cu(I) dioxygen (1) (bond lengths longer than 3.5 Å towards the imidazole ring and towards the amine nitrogen trans to the initial empty coordination position). Only the latter bond is clearly broken in models 2 and 3.…”

Section: Methodsmentioning

confidence: 99%

Dioxygen Activation by Copper-Bleomycin: Theoretical Considerations

Silaghi-Dumitrescu¹,

Surducan²,

Papp³

2014

Croat. Chem. Acta

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Abstract. Density functional theory (DFT) calculations are employed to calculate probable reaction intermediates in dioxygen activation by bleomycin-ligated copper -Cu(I)-dioxygen, Cu(I)-superoxo and Cu(II)-hydroperoxo. The electronic structures of these intermediates are discussed with emphasis on their electromerism. Importantly, unlike in dioxygen activation by iron-bleomycin, formation of these reactive intermediates requires that some of the copper-bleomycin bonds be broken. (doi: 10.5562/cca1793)

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“…MC was isolated from Streptomyces caespitosus and used in treating several cancers including gastric cancer, anal and colon cancer, breast cancer, nonsmall cell lung cancer, head and neck cancer, small bladder papillomas, pancreatic cancer, and cervical cancer. 22 Since MC is an alkylating agent that binds to DNA, causing cross-linking and inhibition of DNA synthesis, there have been some studies on the electrochemical monitoring of MC-DNA interaction. 6,17,22−27 After interaction with DNA, MC was reduced and then 2 Nalkylations followed this reductive activation.…”

Section: −7mentioning

confidence: 99%

Electrochemical monitoring of the interaction between mitomycin C and DNA at chitosan--carbon nanotube composite modified electrodes

Canavar¹,

Ekşin²,

Erdem³

2015

Turk J Chem

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Single-walled carbon nanotube (CNT) and chitosan composite (chitosan*CNT) based sensors were developed as DNA biosensors, and then they were applied for electrochemical investigation of the interaction between the anticancer drug mitomycin C (MC) and DNA. The oxidation signals of MC and guanine were monitored before and after the interaction process by differential pulse voltammetry (DPV). The DPV results were in good agreement with those of electrochemical impedance spectroscopy (EIS). Analytical parameters such as DNA concentration, MC concentration, and MC interaction time with DNA were optimized. The detection limits were 6.85 µ g/mL for DNA and 11.01 µ g/mL for MC.

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The Mitomycin C (MMC)-binding Protein from MMC-producing Microorganisms Protects from the Lethal Effect of Bleomycin: Crystallographic Analysis to Elucidate the Binding Mode of the Antibiotic to the Protein

Cited by 43 publications

References 27 publications

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

Dioxygen Activation by Copper-Bleomycin: Theoretical Considerations

Electrochemical monitoring of the interaction between mitomycin C and DNA at chitosan--carbon nanotube composite modified electrodes

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