Damage of the kinesin heavy chain gene contributes to the antagonism of cisplatin and paclitaxel

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000090042100060&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1791-7530
Externe Identifier
  • Clarivate Analytics Document Solution ID: 367BQ
  • PubMed Identifier: 11062745
ISSN
0250-7005
Ausgabe der Veröffentlichung
5A
Zeitschrift
ANTICANCER RESEARCH
Schlüsselwörter
  • antisense oligodeoxynucleotides
  • apoptosis
  • chemotherapy
  • DNA damage
Paginierung
3211 - 3219
Datum der Veröffentlichung
2000
Status
Published
Titel
Damage of the kinesin heavy chain gene contributes to the antagonism of cisplatin and paclitaxel
Sub types
  • Article
Ausgabe der Zeitschrift
20

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
Paclitaxel (TAX) and cisplatin (DDP) rank among the most promising anti-neoplastic agents for the treatment of epithelial cancer. Pre-clinical and clinical data show that the cytotoxicity resulting from the combined use of TAX and DDP is governed by the order (TAX prior DDP) > (DDP prior TAX). Since this also occurs with DNA damaging agents other than DDP, damage of a sensitivity gene may be of importance. Recently, a role of kinesin heavy chain (KHC) was uncovered for the cytotoxicity of many natural drug derivatives by use of genetic suppressor elements (Gudkov et al. (1994) Proc. Natl. Acad. Sci. USA, 91, 3744-3748). We first confirmed the dependency on the order of addition for TAX and DDP in human leukemic K562 cells taking apoptotic fraction and cell growth as endpoints. We then inhibited KHC gene expression by antisense oligodeoxy-nucleotides or KHC protein function by monoclonal antibody SUK4. Both approaches led to a reduced cytotoxicity of TAX indicating that KHC may confer sensitivity to TAX. Using a PCR-stop assay, we found that DDP indeed caused dose related DNA damage in the KHC gene. There was more DNA damage in the KHC gene than in four other genes (AFP, G6PD, MDR1, TCR-delta). Increasing doses of DDP down-regulated KHC mRNA expression more than of G6PD. There may therefore be a role of KHC for the use of TAX and DDP in combination.
Addresses
  • Department for Internal Medicine IV, University Hospital, RWTH Aachen, Germany. tseffert@viro.med.uni-erlangen.de
Autoren
eISSN
1791-7530
Externe Identifier
  • PubMed Identifier: 11062745
Open access
false
ISSN
0250-7005
Ausgabe der Veröffentlichung
5A
Zeitschrift
Anticancer research
Schlüsselwörter
  • K562 Cells
  • Humans
  • DNA Damage
  • Cisplatin
  • Paclitaxel
  • Oligonucleotides, Antisense
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Cell Division
  • Apoptosis
  • Drug Antagonism
  • Kinesins
Sprache
eng
Medium
Print
Paginierung
3211 - 3219
Datum der Veröffentlichung
2000
Status
Published
Datum der Datenerfassung
2000
Titel
Damage of the kinesin heavy chain gene contributes to the antagonism of cisplatin and paclitaxel.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
20

Data source: Europe PubMed Central

Abstract
Paclitaxel (TAX) and cisplatin (DDP) rank among the most promising anti-neoplastic agents for the treatment of epithelial cancer. Pre-clinical and clinical data show that the cytotoxicity resulting from the combined use of TAX and DDP is governed by the order (TAX prior DDP) > (DDP prior TAX). Since this also occurs with DNA damaging agents other than DDP, damage of a sensitivity gene may be of importance. Recently, a role of kinesin heavy chain (KHC) was uncovered for the cytotoxicity of many natural drug derivatives by use of genetic suppressor elements (Gudkov et al. (1994) Proc. Natl. Acad. Sci. USA, 91, 3744-3748). We first confirmed the dependency on the order of addition for TAX and DDP in human leukemic K562 cells taking apoptotic fraction and cell growth as endpoints. We then inhibited KHC gene expression by antisense oligodeoxy-nucleotides or KHC protein function by monoclonal antibody SUK4. Both approaches led to a reduced cytotoxicity of TAX indicating that KHC may confer sensitivity to TAX. Using a PCR-stop assay, we found that DDP indeed caused dose related DNA damage in the KHC gene. There was more DNA damage in the KHC gene than in four other genes (AFP, G6PD, MDR1, TCR-delta). Increasing doses of DDP down-regulated KHC mRNA expression more than of G6PD. There may therefore be a role of KHC for the use of TAX and DDP in combination.
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/11062745
ISSN
0250-7005
Ausgabe der Veröffentlichung
5A
Zeitschrift
Anticancer Res
Schlüsselwörter
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Apoptosis
  • Cell Division
  • Cisplatin
  • DNA Damage
  • Drug Antagonism
  • Humans
  • K562 Cells
  • Kinesins
  • Oligonucleotides, Antisense
  • Paclitaxel
Sprache
eng
Country
Greece
Paginierung
3211 - 3219
Datum der Veröffentlichung
2000
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2000
Titel
Damage of the kinesin heavy chain gene contributes to the antagonism of cisplatin and paclitaxel.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
20

Data source: PubMed

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