Premature senescence induced by DNA demethylating agent (Decitabine) as therapeutic option for malignant pleural mesothelioma

Amatori, Stefano; Bagaloni, Irene; Viti, Dana; Fanelli, Mirco

doi:10.1016/j.lungcan.2010.10.016

Cited by 28 publications

(19 citation statements)

References 12 publications

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“…A C C E P T E D ACCEPTED MANUSCRIPT 13 nucleoside analogues inducing senescence such as toyocamycin and decitabine, it is rare to identify purine analogues as a senescence-inducing drug candidate [30,31]. …”

Section: Resultsmentioning

confidence: 99%

“…(28)(29)(30)(31)(32)(33)(34)(36)(37)(38)(39)(40)(41) were synthesized and their anti-cancer activities were identified. Among these 36 compounds, N 6 -(4-trifluoromethylphenyl)piperazine derivative(17) without any substitution at N-9 position and its 9-(p-toluene-sulfonyl)/9-cyclopentyl analogues(28,36) were further analyzed for their activity against a hepatocellular carcinoma(HCC) panel due to their promising cytotoxicities.…”

mentioning

confidence: 99%

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Synthesis of novel substituted purine derivatives and identification of the cell death mechanism

Demir

Güven

Özbey

et al. 2015

European Journal of Medicinal Chemistry

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Novel 9-(substituted amino/piperazinoethyl)adenines (4-12), 6-(substituted piperazino/amino)purines (15-27), 9-(p-toluenesulfonyl/cyclopentyl/ethoxycarbonylmethyl)-6-(substituted amino/piperazino)purines (28-34, 36, 37, 38-41) were synthesized and evaluated initially for their cytotoxic activities on liver Huh7, breast T47D and colon HCT116 carcinoma cells. N(6)-(4-Trifluoromethylphenyl)piperazine derivative (17) and its 9-(p-toluene-sulfonyl)/9-cyclopentyl analogues (28, 36) had promising cytotoxic activities. Compounds 17, 28 and 36 were further analysed for their cytotoxicity in a panel of a liver cancer cell lines. The compound 36 had better cytotoxic activities (IC50 ≤ 1 μM) than the nucleobase 5-FU and nucleosides fludarabine, cladribine, and pentostatine on Huh7 cells. Cytotoxicity induced by 36 was later identified as senescence associated cell death by SA-β-Gal assay.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Synthesis of novel substituted purine derivatives and identification of the cell death mechanism

Demir

Güven

Özbey

et al. 2015

European Journal of Medicinal Chemistry

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“…Relatively low extent of apoptotic changes in comparison with high-treatment cytotoxicity and persistence of PI-positive cell fraction in the presence of caspase inhibitors indicate that another type of cell death is induced in parallel with the apoptosis in HL-60 cells. ROS formation, p21WAF1 gene and protein induction, cell cycle arrest, and also DAC-induced increase of cell volume imply possible role of senescence [47–49], the mechanism of DAC action which has been observed in prostate cancer cells [50] or in malignant pleural mesothelioma [51]. Induction of senescence has been detected also in SAHA-treated colon cancer cells with nonfunctioning p21WAF1 or p53 genes [52].…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment with Low Concentrations of Decitabine and SAHA Causes Cell Death in Leukemic Cell Lines but Not in Normal Peripheral Blood Lymphocytes

Brodská

Holoubek

Otevřelová

et al. 2013

BioMed Research International

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Epigenetic therapy reverting aberrant acetylation or methylation offers the possibility to target preferentially tumor cells and to preserve normal cells. Combination epigenetic therapy may further improve the effect of individual drugs. We investigated combined action of demethylating agent decitabine and histone deacetylase inhibitor SAHA (Vorinostat) on different leukemic cell lines in comparison with peripheral blood lymphocytes. Large decrease of viability, as well as huge p21WAF1 induction, reactive oxygen species formation, and apoptotic features due to combined decitabine and SAHA action were detected in leukemic cell lines irrespective of their p53 status, while essentially no effect was observed in response to the combined drug action in normal peripheral blood lymphocytes of healthy donors. p53-dependent apoptotic pathway was demonstrated to participate in the wtp53 CML-T1 leukemic cell line response, while significant influence of reactive oxygen species on viability decrease has been detected in p53-null HL-60 cell line.

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“…After 24 hours of treatment with the reported concentrations of maltonis, cells were stained with anti-phospho-H2AX antibody (Cell Signaling, Danvers, MA,) and counterstained with DAPI as previously described [32]. Confocal images were acquired with Leica TCS SP2, magnification 63X (Wetzlar, Germany).…”

Section: Methodsmentioning

confidence: 99%

An aza-macrocycle containing maltolic side-arms (maltonis) as potential drug against human pediatric sarcomas

et al. 2014

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Premature senescence induced by DNA demethylating agent (Decitabine) as therapeutic option for malignant pleural mesothelioma

Cited by 28 publications

References 12 publications

Synthesis of novel substituted purine derivatives and identification of the cell death mechanism

Synthesis of novel substituted purine derivatives and identification of the cell death mechanism

Combined Treatment with Low Concentrations of Decitabine and SAHA Causes Cell Death in Leukemic Cell Lines but Not in Normal Peripheral Blood Lymphocytes

An aza-macrocycle containing maltolic side-arms (maltonis) as potential drug against human pediatric sarcomas

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