Effect of 5-Aza-2’-deoxycytidine on immune-associated proteins in exosomes from hepatoma

Wu, Xiao; Sanren, Gao-Wa; Zhu, Junzhen; Li, Qiu-Wen; Kang, Huanrong; Wang, Ruliang; Lin-ping, Song; Ye, Ming

doi:10.3748/wjg.v16.i19.2371

Cited by 20 publications

(18 citation statements)

References 25 publications

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“…Previous studies reported that some miRNAs were selectively secreted into exosomes. 18,28,29) However, the intracellular expression levels of miR-200c and miR-141 positively correlated with their exosomal expression levels in this study, suggesting that miR-200c and miR-141 were not selectively incorporated into exosomes.…”

Section: Discussioncontrasting

confidence: 53%

“…17) Furthermore, increases in the expression levels of miR-200 family members have been reported in highly invasive cancer cells and their exosomes. 18) Although exosomal proteins, such as human leucocyte antigen-1, were previously found to be increased by DAC, 19) changes in the exosomal ex-pression levels of miRNAs from CRC cells by DAC have not yet been reported.…”

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confidence: 99%

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Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Tanaka

Hosokawa

Iwakawa

2015

Biological & Pharmaceutical Bulletin

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The effects of decitabine (DAC), a DNA methyltransferase (DNMT) inhibitor, on metastasis and exosomal expression of microRNAs were examined in SW620/OxR cells, a human colorectal cancer (CRC) cell line (SW620) with acquired resistance to oxaliplatin. This cell line shows an invasive phenotype by epithelial-mesenchymal transition. Two CRC cell lines, SW480, derived from primary CRC, and SW620, derived from lymph node metastasis, which were obtained from the same patient, as well as SW620/OxR, were also used in the present study. Cytarabine (Ara-C), a non-DNMT-inhibiting cytidine analog, was used as negative control of DAC. No significant difference was observed in the invasion abilities of SW480 cells treated with DAC or Ara-C. On the other hand, invasion ability was suppressed by treatment with DAC in SW620 and SW620/OxR cells. Up-regulated expression of E-cadherin, microRNA-200c (miR-200c), and miR-141 following DAC treatment indicated the acquisition of epithelial cell-like characteristics in SW620 and SW620/OxR cells. Exosomal expression levels of miR-200c and miR-141 were also up-regulated by DAC treatment in SW620 and SW620/OxR but not in SW480 cells. This increase in exosomal miRNA expression negatively correlated with invasion ability. These results suggest that DNA demethylation treatment caused acquisition of epithelial cell-like characteristics in SW620 and SW620/OxR cells. Furthermore, the observed increased exosomal expression of miR-200c and miR-141 may be an indicator or biomarker candidate for mesenchymal-epithelial transition of CRC cells.

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Section: Discussioncontrasting

confidence: 53%

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confidence: 99%

Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Tanaka

Hosokawa

Iwakawa

2015

Biological & Pharmaceutical Bulletin

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“…However, the fact that a tripeptide is sufficient to block the Fas/Fap1 interaction suggests that a small molecule might be developed with the same effect. Additionally, increased Fap1 has also been associated with Fas resistance in colon cancer, suggesting wider applications for targeting the Fap1/Fas interaction [33,34]. These are areas of interest for future investigations.…”

Section: Discussionmentioning

confidence: 99%

Fas-associated phosphatase 1 mediates Fas resistance in myeloid progenitor cells expressing the Bcr–abl oncogene

Huang

Bei

Eklund

2012

Leukemia & Lymphoma

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The interferon consensus sequence binding protein (Icsbp) is a transcription factor that influences multiple aspects of myelopoiesis. Expression of Icsbp is decreased in the bone marrow of human subjects with chronic myeloid leukemia (CML), and studies in murine models suggest that Icsbp functions as an anti-oncogene for CML. We previously identified a set of Icsbp target genes that may contribute to this anti-oncogene effect. The set includes PTPN13, the gene encoding Fas-associated phosphatase 1 (Fap1, a Fas antagonist). We previously demonstrated that myeloid progenitor cells from Icsbp-knockout mice exhibit Fap1-dependent Fas resistance. In the present study, we determined that the Fas resistance of Bcr−abl+ cells is Icsbp- and Fap1-dependent. We also found that treatment of Bcr−abl+ bone marrow cells with a Fap1-blocking peptide prevents in vitro selection of a tyrosine kinase inhibitor (TKI)-resistant population. Therefore, these results have implications for therapeutic targeting of the Fas-resistant leukemia stem cell population and addressing TKI resistance in CML.

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“…5-AZA-CdR reactivates the tumor suppressor gene VHL in human renal carcinoma cell lines and the expression of the p16/CDKN2 tumor suppressor gene, which prevents the entry of tumor cells into the S-phase of the cell cycle, in different tumor cell lines [20,68-72]. The mRNA expression of the p53 gene increases in hepatoma cell lines after treatment with 5-AZA-CdR [73]. Methylation of hMLH1, a mismatch repair gene that confers chemoresistance to certain anticancer agents, is reactivated by 5-AZA-CdR in ovarian and colon cancer cell lines [74,75].…”

Section: In Vitro Antineoplastic Actionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic analysis of 5-aza-2’-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy

2013

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5-Aza-2′-deoxycytidine (5-AZA-CdR, decitabine), an epigenetic drug that inhibits DNA methylation, is currently used to treat myelodysplastic syndrome (MDS), and is under investigation for treating acute myeloid leukemia (AML) and other malignancies. 5-AZA-CdR can reactivate tumor suppressor genes silenced by aberrant DNA methylation, a frequent event in all types of cancer. Because this epigenetic change is reversible, it is a good target for 5-AZA-CdR therapy. We have reviewed the preclinical data of 5-AZA-CdR to analyze the concentrations and exposure times required to eradicate cancer stem cells. We analyzed the dose-schedules used in animal models that show potent antineoplastic activity of 5-AZA-CdR. We attempted to correlate the preclinical data with the responses obtained in clinical trials of 5-AZA-CdR in patients with cancer. The pharmacokinetics and drug distribution of 5-AZA-CdR are key parameters because adequate therapeutic drug levels are required to eliminate cancer stem cells in all anatomic compartments. The plasma half-life of 5-AZA-CdR in humans is approximately 20 minutes due to the high levels in the liver of cytidine deaminase, the enzyme that inactivates this analogue. This provides a rationale to use an inhibitor of cytidine deaminase in combination with 5-AZA-CdR. Low-dose 5-AZA-CdR is effective for MDS and AML and can induce complete remissions (CR). However, maintenance of CR with low-dose 5-AZA-CdR is difficult. Based on analyses of preclinical and clinical data, low dose 5-AZA-CdR has the potential to be an effective form of therapy in some patients with cancer. For patients who do not respond to low dose therapy we recommend dose-intensive treatment with 5-AZA-CdR. Patients who are candidates for intensive dose 5-AZA-CdR should have a good bone marrow status so as to permit adequate recovery from myelosuppression, the major toxicity of 5-AZA-CdR. Solid tumors are also interesting targets for therapy with 5-AZA-CdR. Both low dose and intensive therapy with 5-AZA-CdR can reduce the proliferative potential of tumor stem cells in animal models. We propose novel dose schedules of 5-AZA-CdR for investigation in patients with cancer. The full chemotherapeutic potential of 5-AZA-CdR to treat cancer merits further clinical investigation and can only be realized when its optimal dose-schedule is determined.

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Effect of 5-Aza-2’-deoxycytidine on immune-associated proteins in exosomes from hepatoma

Abstract: RNA interference combined with conventional chemotherapy is more effective against colon cancer.

Cited by 20 publications

References 25 publications

Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Fas-associated phosphatase 1 mediates Fas resistance in myeloid progenitor cells expressing the Bcr–abl oncogene

Pharmacokinetic and pharmacodynamic analysis of 5-aza-2’-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy

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