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Cancer Chemotherapy and Biological... 1996
Review
Topics: Animals; Antibiotics, Antineoplastic; Cell Hypoxia; Drug Resistance, Neoplasm; Drug Therapy, Combination; Humans; Mitomycin; Mitomycins; Neoplasms; Oxidation-Reduction
PubMed: 8639396
DOI: No ID Found -
Cancer Chemotherapy and Biological... 1999
Review
Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Biotransformation; DNA Damage; Drug Interactions; Fanconi Anemia; Humans; Mitomycin
PubMed: 10800477
DOI: No ID Found -
Cancer Chemotherapy and Biological... 1997
Review
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; DNA Damage; Drug Resistance, Neoplasm; Humans; Mitomycin; Signal Transduction
PubMed: 9551208
DOI: No ID Found -
Chemical Record (New York, N.Y.) Jan 2023Mitomycin C, (MC), an antitumor drug used in the clinics, is a DNA alkylating agent. Inert in its native form, MC is reduced to reactive mitosenes in cellulo which... (Review)
Review
Mitomycin C, (MC), an antitumor drug used in the clinics, is a DNA alkylating agent. Inert in its native form, MC is reduced to reactive mitosenes in cellulo which undergo nucleophilic attack by DNA bases to form monoadducts as well as interstrand crosslinks (ICLs). These properties constitute the molecular basis for the cytotoxic effects of the drug. The mechanism of DNA alkylation by mitomycins has been studied for the past 30 years and, until recently, the consensus was that drugs of the mitomycins family mainly target CpG sequences in DNA. However, that paradigm was recently challenged. Here, we relate the latest research on both MC and dicarbamoylmitomycin C (DMC), a synthetic derivative of MC which has been used to investigate the regioselectivity of mitomycins DNA alkylation as well as the relationship between mitomycins reductive activation pathways and DNA adducts stereochemical configuration. We also review the different synthetic routes to access mitomycins nucleoside adducts and oligonucleotides containing MC/DMC DNA adducts located at a single position. Finally, we briefly describe the DNA structural modifications induced by MC and DMC adducts and how site specifically modified oligonucleotides have been used to elucidate the role each adduct plays in the drugs cytotoxicity.
Topics: DNA Adducts; Mitomycin; DNA; Oligonucleotides
PubMed: 36251922
DOI: 10.1002/tcr.202200193 -
Bioorganic Chemistry Jun 2022While interstrand crosslinks (ICLs) have been considered as one type of DNA damage in the past, there is mounting evidence suggesting that these highly cytotoxic lesions...
While interstrand crosslinks (ICLs) have been considered as one type of DNA damage in the past, there is mounting evidence suggesting that these highly cytotoxic lesions are processed differently by the cellular machinery depending upon the ICL structure. In this study, we examined the crosslinking ability of three mitomycins, the structure of the ICLs they produce and the cytotoxicity of the drugs toward three different cell lines. The drugs are: mitomycin C (1), decarbamoylmitomycin C (2), and a mitomycin-conjugate (3) whose mitosane moiety is linked to a N-methylpyrrole carboxamide. We found that, overall, both MC and compound 3 show strong similarities regarding their alkylation of DNA, while DMC alkylating behavior is markedly different. To gain further insight into the mode of action of these drugs, we performed high throughput gene expression and gene ontology analysis to identify gene expression and cellular pathways most impacted by each drug treatment in MCF-7 cell lines. We observed that the novel mitomycin derivative (3) specifically causes changes in the expression of genes encoding proteins involved in cell integrity and tissue structure. Further analysis using bioinformatics (IPA) indicated that the new derivative (3) displays a stronger downregulation of major signaling networks that regulate the cell cycle, DNA damage response and cell proliferation when compared to MC and DMC. Collectively, these findings demonstrate that cytotoxic mechanisms of all three drugs are complex and are not solely related to their crosslinking abilities or the structure of the ICLs they produce.
Topics: Alkylation; DNA; DNA Adducts; DNA Damage; Humans; Mitomycin; Mitomycins
PubMed: 35349830
DOI: 10.1016/j.bioorg.2022.105744 -
Urologia Oct 2016If we think about the launch date of Mitomycin C, we could think that this supplement is very much focused on history of Medicine, and, yes, Mitomycin certainly has been...
If we think about the launch date of Mitomycin C, we could think that this supplement is very much focused on history of Medicine, and, yes, Mitomycin certainly has been a main contributor to the history of Urology. However, it is even more striking to think that even after fifty years of its use by Urologists worlwide, Mitomycin C remains an absolute "Must". The simplicity of use, the efficacy and the tolerability of Mitomycin explain its established role. In fact, "long standing" does not mean "old". The new technologies, introduced progressively in the last decades, have fully confirmed the present and future role of this drug, that is well illustrated in the articles contained in this supplement. I hope you will enjoy reading it and (re)discovering Mitomycin C.
Topics: Humans; Mitomycin
PubMed: 27768212
DOI: 10.5301/RU.2016.16271 -
Cancer Chemotherapy and Biological... 1992
Review
Topics: Animals; Biotransformation; Humans; Hydrogen-Ion Concentration; Mitomycin; Mitomycins; NAD(P)H Dehydrogenase (Quinone)
PubMed: 1389922
DOI: No ID Found -
Journal of Medicinal Chemistry Jan 1986The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and... (Comparative Study)
Comparative Study
The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these complexes had antitumor activity in mice. However, they were less active than mitomycin C. Weak associations between mitomycin C and metal ions were demonstrated by 13C and 15N NMR spectrometry.
Topics: Animals; Chemical Phenomena; Chemistry; Chlorides; Copper; Leukemia P388; Magnetic Resonance Spectroscopy; Mice; Mitomycin; Mitomycins; Platinum; Platinum Compounds; Zinc; Zinc Compounds
PubMed: 3079830
DOI: 10.1021/jm00151a023 -
Cancer Chemotherapy and Biological... 1991
Review
Topics: Animals; Combined Modality Therapy; Humans; Mitomycin; Neoplasms
PubMed: 1931457
DOI: No ID Found -
Bioorganic Chemistry Jun 2013The anticancer drug mitomycin C produces cytotoxic effects after being converted to a highly reactive bis-electrophile by a reductive activation, a reaction that a...
The anticancer drug mitomycin C produces cytotoxic effects after being converted to a highly reactive bis-electrophile by a reductive activation, a reaction that a number of 1-electron or 2-electron oxidoreductase enzymes can perform in cells. Several reports in the literature indicate that ascorbic acid can modulate the cytotoxic effects of mitomycin C, either potentiating or inhibiting its effects. As ascorbic acid is a reducing agent that is known to be able to reduce quinones, it could be possible that the observed modulatory effects are a consequence of a direct redox reduction between mitomycin C and ascorbate. To determine if this is the case, the reaction between mitomycin C and ascorbate was studied using UV/Vis spectroscopy and LC/MS. We also studied the reaction of ascorbate with mitomycin A, a highly toxic member of the mitomycin family with a higher redox potential than mitomycin C. We found that ascorbate is capable to reduce mitomycin A efficiently, but it reduces mitomycin C rather inefficiently. The mechanisms of activation have been elucidated based on the kinetics of the reduction and on the analysis of the mitosene derivatives formed after the reaction. We found that the activation occurs by the interplay of three different mechanisms that contribute differently, depending on the pH of the reaction. As the reduction of mitomycin C by ascorbate is rather inefficiently at physiologically relevant pH values we conclude that the modulatory effect of ascorbate on the cytotoxicity of mitomycin C is not the result of a direct redox reaction and therefore this modulation must be the consequence of other biochemical mechanisms.
Topics: Animals; Ascorbic Acid; CHO Cells; Cell Survival; Cricetinae; Cricetulus; Hydrogen-Ion Concentration; Kinetics; Mitomycin; Mitomycins; Oxidation-Reduction; Quinones; Spectrophotometry, Ultraviolet
PubMed: 23639828
DOI: 10.1016/j.bioorg.2013.03.002