Abstract：
:The reaction mechanism of DNA topoisomerase II (TOP2) involves a covalent double-strand break intermediate in which the enzyme is coupled to DNA via a 5'-phosphotyrosyl bond. This normally transient enzyme-bridged break is stabilised by drugs such as mitoxantrone, mAMSA, etoposide, doxorubicin, epirubicin and idarubicin, which are referred to as TOP2 poisons. Removal of topoisomerase II by the proteasome is involved in the repair of these lesions. In K562 cells, inhibiting the proteasome with MG132 significantly potentiated the growth inhibition by these six drugs that target topoisomerase II, and the highest level of potentiation was observed with mitoxantrone. Mitoxantrone also showed the greatest potentiation by MG132 in three Nalm 6 cell lines with differing levels of TOP2A or TOP2B. Mitoxantrone was also potentiated by the clinically used proteasome inhibitor PS341 (Velcade). We have also shown that proteasome inhibition with MG132 in K562 cells reduces the rate of removal of mitoxantrone or etoposide stabilised topoisomerase complexes from DNA, suggesting a possible mechanism for the potentiation of topoisomerase II drugs by proteasomal inhibition.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lee KC,Bramley RL,Cowell IG,Jackson GH,Austin CAdoi
10.1016/j.bcp.2015.12.015subject
Has Abstractpub_date
2016-03-01 00:00:00pages
29-39eissn
0006-2952issn
1873-2968pii
S0006-2952(15)00790-Xjournal_volume
103pub_type
杂志文章abstract：:Alone and in synergistic combination with retinoids, dietary glucarate inhibits both the chemical induction and growth of rat mammary tumors. To investigate the pharmacokinetics of glucarate, [14C]glucarate was synthesized, converted to the calcium salt, and administered to rats bearing primary mammary tumors. When gi...
journal_title：Biochemical pharmacology
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
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journal_title：Biochemical pharmacology
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更新日期：1985-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：1995-11-27 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.bcp.2011.12.006
更新日期：2012-04-01 00:00:00
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pub_type： 杂志文章
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更新日期：1996-06-14 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90405-8
更新日期：1985-06-15 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2017-01-15 00:00:00
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更新日期：1984-06-01 00:00:00
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pub_type： 杂志文章
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更新日期：1999-05-01 00:00:00
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更新日期：1992-10-06 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2005-03-01 00:00:00
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journal_title：Biochemical pharmacology
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更新日期：1982-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90144-a
更新日期：1990-02-15 00:00:00
abstract：BACKGROUND AND PURPOSE:Chronic nicotine exposure upregulates α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The goal of this study was to examine the role of three serine residues in the large cytoplasmic loop of the α4 subunit on α4β2* upregulation in neurons. EXPERIMENTAL APPROACH:Serine residues S33...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.11.008
更新日期：2019-01-01 00:00:00
abstract：:The formation of triacylglycerols containing fenoprofen was studied in rat isolated adipocytes and hepatocytes incubated with [3H]glycerol and R or S fenoprofen. In both hepatocytes and adipocytes there was a high-affinity enzymatic process for the synthesis of triacylglycerol containing fenoprofen which was stereospe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90537-0
更新日期：1988-05-15 00:00:00
