Influence OF anticancer drugs on DNA methylation in liver of female mice

Hanafy, Shaden Muawia; Salem, Tarek A E; El-Aziz, Amal Ahmed Abd; El-Fiky, Bahgat A.; Shokair, Mahmoud Abd El-Azeim

doi:10.4236/ajmb.2011.12008

Cited by 4 publications

(5 citation statements)

References 21 publications

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“…5), because SAH inhibits transmethylation reactions. This result is consistent with previous reports that perturbing folate and C1 metabolism affects global DNA methylation (15,17,32,48,76,78,79). Perhaps as a result of decreased DNA methylation, several key pluripotency genes such as OCT4, SOX2, and SSEA4 are expressed in FPGS ko cells (Fig.…”

Section: Discussionsupporting

confidence: 93%

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Elimination of human folypolyglutamate synthetase alters programming and plasticity of somatic cells

et al. 2019

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Folates are vital cofactors for the regeneration of S-adenosyl methionine, which is the methyl source for DNA methylation, protein methylation, and other aspects of one-carbon (C1) metabolism. Thus, folates are critical for establishing and preserving epigenetic programming. Folypolyglutamate synthetase (FPGS) is known to play a crucial role in the maintenance of intracellular folate levels. Therefore, any modulation in FPGS is expected to alter DNA methylation and numerous other metabolic pathways. To explore the role of polyglutamylation of folate, we eliminated both isoforms of FPGS in human cells (293T), producing FPGS knockout (FPGS ko ) cells. The elimination of FPGS significantly decreased cell proliferation, with a major effect on oxidative phosphorylation and a lesser effect on glycolysis. We found a substantial reduction in global DNA methylation and noteworthy changes in gene expression related to C1 metabolism, cell division, DNA methylation, pluripotency, Glu metabolism, neurogenesis, and cardiogenesis. The expression levels of NANOG, octamer-binding transcription factor 4, and sex-determining region Y-box 2 levels were increased in the mutant, consistent with the transition to a stem cell-like state. Gene expression and metabolite data also indicate a major change in Glu and GABA metabolism. In the appropriate medium, FPGS ko cells can differentiate to produce mainly cells with characteristics of either neural stem cells or cardiomyocytes.-

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Section: Discussionsupporting

confidence: 93%

“…A global decrease in methylated DNA content has previously been observed after treatment with antifolates (15, 18, 19, 47, 48). Therefore, we measured the global level of 5‐mC in FPGS ko cells and found a significant reduction in FPGS ko cells ( Fig .…”

Section: Resultsmentioning

confidence: 75%

Elimination of human folypolyglutamate synthetase alters programming and plasticity of somatic cells

et al. 2019

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“…Evidence has proved that anticancer drugs with DOX can act as DNA hypomethylating agents. According to Hanafy et al (4), total methylation percentage was markedly reduced from 62.2 (control) to 36.7% by the action of DOX. SP1049C, a Pluronic-based micellar formulation of DOX, significantly increased gene promoter demethylation compared to saline control P388 cancer stem cells in vivo (38).…”

Section: Discussionmentioning

confidence: 95%

“…DOX also reacts with cellular formaldehyde to form DNA adducts (3). To effectively utilize the antitumor function of DOX, there have been few studies focusing on the other mechanisms of DOX (4).…”

Section: Introductionmentioning

confidence: 99%

Combination treatment with doxorubicin and microRNA-21 inhibitor synergistically augments anticancer activity through upregulation of tumor suppressing genes

Zhang

Han

Wei

et al. 2015

International Journal of Oncology

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Doxorubicin (DOX) is a key chemotherapeutic drug for cancer treatment. The antitumor mechanism of DOX is its action as a topoisomerase II poison by preventing DNA replication. Our study shows that DOX can be involved in epigenetic regulation of gene transcription through downregulation of DNA methyltransferase 1 (DNMT1) then reactivation of DNA methylation-silenced tumor suppressor genes in glioblastoma (GBM). Recent evidence demonstrated that microRNA (miR or miRNA) can mediate expression of genes through post-transcriptional regulation and modulate sensitivity to anticancer drugs. As one of the first miRNAs detected in the human genome, miR-21 has been validated to be overexpressed in GBM. Combination treatment of a chemotherapeutic and miRNA showed synergistically increased anticancer activities which has been proven to be an effective strategy for tumor therapy. In our study, co-treatment of DOX and miR-21 inhibitor (miR-21i) resulted in remarkably increased expression of tumor suppressor genes compared with DOX or the miR-21i treatment alone. Moreover, we demonstrate that combining DOX and miR-21i significantly reduced tumor cell proliferation, invasion and migration in vitro. Our study concludes that combining DOX and miR-21i is a new strategy for the therapy of GBM.

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“…So, there are many Cancer Chemother Pharmacol data demonstrating that chemotherapy agents decrease DNA methylation and inhibit activity of histone deacetylases [43][44][45] that can make MDR gene promoters accessible and competent for subsequent transcriptional activation. Different mechanisms of induction of DNA hypomethylation by chemotherapeutic drugs have been described in the recent review [45].…”

Section: Cancer Chemother Pharmacolmentioning

confidence: 99%

Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response

Litviakov¹,

Чердынцева

Цыганов

et al. 2012

Cancer Chemother Pharmacol

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Influence OF anticancer drugs on DNA methylation in liver of female mice

Cited by 4 publications

References 21 publications

Elimination of human folypolyglutamate synthetase alters programming and plasticity of somatic cells

Elimination of human folypolyglutamate synthetase alters programming and plasticity of somatic cells

Combination treatment with doxorubicin and microRNA-21 inhibitor synergistically augments anticancer activity through upregulation of tumor suppressing genes

Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response

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