Abstract：
BACKGROUND/AIM:Forodesine inhibits purine nucleoside phosphorylase, resulting in an accumulation of intracellular dGTP and consequently cell death. 9-β-D-Arabinofuranosylguanine (ara-G) is an active compound of nelarabine that is intracellularly phosphorylated to a triphosphate form, which inhibits DNA synthesis. Both agents show cytotoxicity toward T-cell malignancies. In the present study, we investigated the cytotoxicity of forodesine in vitro using ara-G-resistant leukemia cells. MATERIALS AND METHODS:T-Lymphoblastic leukemia cell line CCRF-CEM and ara-G-resistant CEM variant cell line CEM/ara-G that we had previously established were used. RESULTS:A growth-inhibition assay demonstrated that CEM cells were insensitive to single-agent forodesine treatment. The cells were also insensitive to deoxyguanosine at a maximal concentration of 10 μM. CEM/ara-G cells were 80-fold more resistant to ara-G than were CEM cells, and the mode of sensitivity to forodesine and deoxyguanosine was similar to that of CEM cells. In the presence of 10 μM deoxyguanosine, forodesine effectively inhibited the growth of CEM cells but not that of CEM/ara-G cells. Flow cytometric analyses showed that combination of forodesine and deoxyguanosine induced apoptosis of CEM cells but not of CEM/ara-G cells. The addition of ara-G did not augment the cytotoxicity of the forodesine/deoxyguanosine combination towards CEM cells or CEM/ara-G cells. The combination index revealed antagonism between forodesine and ara-G. The intracellular production of ara-G triphosphate was reduced in the presence of forodesine. CONCLUSION:Nelarabine-resistant CEM/ara-G cells are insensitive to forodesine.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Yamauchi T,Uzui K,Nishi R,Tasaki T,Ueda Tsubject
Has Abstractpub_date
2014-09-01 00:00:00pages
4885-92issue
9eissn
0250-7005issn
1791-7530pii
34/9/4885journal_volume
34pub_type
杂志文章abstract：BACKGROUND:It is hypothesised that hypermethylation of the CpG island in the promoter region in several tumour suppressor genes contributes one of the mechanisms for silencing or down-regulating the expression of the tumour suppressor genes. One of the putative tumour suppressor genes, the E-cadherin gene, has shown do...
journal_title：Anticancer research
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更新日期：2002-11-01 00:00:00
abstract：PURPOSE:To determine the tolerability and efficacy of the combination of gefitinib with gemcitabine plus vinorelbine in metastatic breast cancer (MBC) patients, pretreated with anthracyclines and taxanes. PATIENTS AND METHODS:Women with measurable MBC pretreated with anthracycline- and taxane-based chemotherapy receiv...
journal_title：Anticancer research
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journal_title：Anticancer research
pub_type： 杂志文章,多中心研究
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journal_title：Anticancer research
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pub_type： 临床试验,杂志文章
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doi：
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