Induction of urokinase-type plasminogen activator by anticancer agents in RC-K8 human lymphoma cells

Misako Shibakura, K. Niiya, T. Kiguchi, Y. Nakata, M. Harada

Research output: Contribution to journalArticle

Abstract

We have shown that the anthracycline antibiotics induce u-PA through the gene expression in which reactive oxygen species (ROS) may be involved. Here, we examined the effects of other ROS inducible anticancer agents, such as mitomycin C (MMC), cisplatin and camptothecin (CPT) on the u-PA expression in RC-K8 human lymphoma cells. u-PA activities were quantitatively measured using a synthetic chromogenic substrate S-2444. All of these agents, especially CPT and SN38, the active metabolite of CPT, increased u-PA accumulation in the conditioned medium in a dose-dependent manner. The peak induction was observed at the sublethal concentrations. The u-PA induction by CPT was also confirmed by the fibrin-zymography. No specific activation of metalloproteinases, MMP-2 and MMP-9, was shown by the gelatin-zymography. Northern blotting using Rl-labeled u-PA cDNA probe revealed that CPT and SN38 increased u-PA mRNA levels. Electrophoretic mobility shift assay revealed that the nuclear protein binding to Rel-related protein-binding element, present in the u-PA promoter, was activated after CPT stimulation. Bindings to AP-1 and CREB elements were not activated. These data suggest that CPT induces u-PA probably through u-PA gene expression by activating NF-kB transcriptional factor. Therefore, the sublethal doses of these anticancer agents may influence many aspects of tumor growth and invasiveness through activating u-PA/plasmin system.

Original languageEnglish
Pages (from-to)16
Number of pages1
JournalFibrinolysis and Proteolysis
Volume14
Issue numberSUPPL. 1
Publication statusPublished - 2000

Fingerprint

Camptothecin
Urokinase-Type Plasminogen Activator
Antineoplastic Agents
Lymphoma
Protein Binding
Transcription Factor RelB
5-oxo-prolyl-glycyl-arginine-4-nitroanilide
Reactive Oxygen Species
Gene Expression
NF-kappa B
Fibrinolysin
Anthracyclines
Matrix Metalloproteinase 2
Transcription Factor AP-1
Mitomycin
Electrophoretic Mobility Shift Assay
Gelatin
Conditioned Culture Medium
Nuclear Proteins
Fibrin

ASJC Scopus subject areas

  • Hematology

Cite this

Induction of urokinase-type plasminogen activator by anticancer agents in RC-K8 human lymphoma cells. / Shibakura, Misako; Niiya, K.; Kiguchi, T.; Nakata, Y.; Harada, M.

In: Fibrinolysis and Proteolysis, Vol. 14, No. SUPPL. 1, 2000, p. 16.

Research output: Contribution to journalArticle

Shibakura, Misako ; Niiya, K. ; Kiguchi, T. ; Nakata, Y. ; Harada, M. / Induction of urokinase-type plasminogen activator by anticancer agents in RC-K8 human lymphoma cells. In: Fibrinolysis and Proteolysis. 2000 ; Vol. 14, No. SUPPL. 1. pp. 16.
@article{48ce7b3ffeb94fa3afa6804107332467,
title = "Induction of urokinase-type plasminogen activator by anticancer agents in RC-K8 human lymphoma cells",
abstract = "We have shown that the anthracycline antibiotics induce u-PA through the gene expression in which reactive oxygen species (ROS) may be involved. Here, we examined the effects of other ROS inducible anticancer agents, such as mitomycin C (MMC), cisplatin and camptothecin (CPT) on the u-PA expression in RC-K8 human lymphoma cells. u-PA activities were quantitatively measured using a synthetic chromogenic substrate S-2444. All of these agents, especially CPT and SN38, the active metabolite of CPT, increased u-PA accumulation in the conditioned medium in a dose-dependent manner. The peak induction was observed at the sublethal concentrations. The u-PA induction by CPT was also confirmed by the fibrin-zymography. No specific activation of metalloproteinases, MMP-2 and MMP-9, was shown by the gelatin-zymography. Northern blotting using Rl-labeled u-PA cDNA probe revealed that CPT and SN38 increased u-PA mRNA levels. Electrophoretic mobility shift assay revealed that the nuclear protein binding to Rel-related protein-binding element, present in the u-PA promoter, was activated after CPT stimulation. Bindings to AP-1 and CREB elements were not activated. These data suggest that CPT induces u-PA probably through u-PA gene expression by activating NF-kB transcriptional factor. Therefore, the sublethal doses of these anticancer agents may influence many aspects of tumor growth and invasiveness through activating u-PA/plasmin system.",
author = "Misako Shibakura and K. Niiya and T. Kiguchi and Y. Nakata and M. Harada",
year = "2000",
language = "English",
volume = "14",
pages = "16",
journal = "Fibrinolysis and Proteolysis",
issn = "1369-0191",
publisher = "Churchill Livingstone",
number = "SUPPL. 1",

}

TY - JOUR

T1 - Induction of urokinase-type plasminogen activator by anticancer agents in RC-K8 human lymphoma cells

AU - Shibakura, Misako

AU - Niiya, K.

AU - Kiguchi, T.

AU - Nakata, Y.

AU - Harada, M.

PY - 2000

Y1 - 2000

N2 - We have shown that the anthracycline antibiotics induce u-PA through the gene expression in which reactive oxygen species (ROS) may be involved. Here, we examined the effects of other ROS inducible anticancer agents, such as mitomycin C (MMC), cisplatin and camptothecin (CPT) on the u-PA expression in RC-K8 human lymphoma cells. u-PA activities were quantitatively measured using a synthetic chromogenic substrate S-2444. All of these agents, especially CPT and SN38, the active metabolite of CPT, increased u-PA accumulation in the conditioned medium in a dose-dependent manner. The peak induction was observed at the sublethal concentrations. The u-PA induction by CPT was also confirmed by the fibrin-zymography. No specific activation of metalloproteinases, MMP-2 and MMP-9, was shown by the gelatin-zymography. Northern blotting using Rl-labeled u-PA cDNA probe revealed that CPT and SN38 increased u-PA mRNA levels. Electrophoretic mobility shift assay revealed that the nuclear protein binding to Rel-related protein-binding element, present in the u-PA promoter, was activated after CPT stimulation. Bindings to AP-1 and CREB elements were not activated. These data suggest that CPT induces u-PA probably through u-PA gene expression by activating NF-kB transcriptional factor. Therefore, the sublethal doses of these anticancer agents may influence many aspects of tumor growth and invasiveness through activating u-PA/plasmin system.

AB - We have shown that the anthracycline antibiotics induce u-PA through the gene expression in which reactive oxygen species (ROS) may be involved. Here, we examined the effects of other ROS inducible anticancer agents, such as mitomycin C (MMC), cisplatin and camptothecin (CPT) on the u-PA expression in RC-K8 human lymphoma cells. u-PA activities were quantitatively measured using a synthetic chromogenic substrate S-2444. All of these agents, especially CPT and SN38, the active metabolite of CPT, increased u-PA accumulation in the conditioned medium in a dose-dependent manner. The peak induction was observed at the sublethal concentrations. The u-PA induction by CPT was also confirmed by the fibrin-zymography. No specific activation of metalloproteinases, MMP-2 and MMP-9, was shown by the gelatin-zymography. Northern blotting using Rl-labeled u-PA cDNA probe revealed that CPT and SN38 increased u-PA mRNA levels. Electrophoretic mobility shift assay revealed that the nuclear protein binding to Rel-related protein-binding element, present in the u-PA promoter, was activated after CPT stimulation. Bindings to AP-1 and CREB elements were not activated. These data suggest that CPT induces u-PA probably through u-PA gene expression by activating NF-kB transcriptional factor. Therefore, the sublethal doses of these anticancer agents may influence many aspects of tumor growth and invasiveness through activating u-PA/plasmin system.

UR - http://www.scopus.com/inward/record.url?scp=33847000280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847000280&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 16

JO - Fibrinolysis and Proteolysis

JF - Fibrinolysis and Proteolysis

SN - 1369-0191

IS - SUPPL. 1

ER -