Involvement of ERK1/2 and p38 MAP kinase in doxorubicin-induced uPA expression in human RC-K8 lymphoma and NCI-H69 small cell lung carcinoma cells

Masami Niiya, Kenji Niiya, Misako Shibakura, Noboru Asaumi, Chikamasa Yoshida, Katsuji Shinagawa, Takanori Teshima, Fumihiko Ishimaru, Kazuma Ikeda, Mitsune Tanimoto

Research output: Contribution to journalArticle

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Abstract

We previously demonstrated the doxorubicin-induced urokinase-type plasminogen activator (uPA) expression in human RC-K8 lymphoma cells and NCI-H69 small cell lung carcinoma cells in which reactive oxygen species might be involved. Western blotting analysis revealed phosphorylation/activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase and stress-activated protein kinase/c-jun N-terminal protein kinase (SAPK/JNK) in doxorubicin-treated RC-K8 and H69 cells, and, therefore, we attempted to identify the MAP kinases implicated in doxorubicin-induced uPA expression by the use of their specific inhibitors. U0126, SB202190 and JNKI-1, inhibitors for MAPK kinase, (MEK) 1/2, p38 MAP kinase and SAPK/JNK, respectively, specifically and clearly inhibited their corresponding kinases. U0126 and SB202190, but not JNKI-1, almost completely inhibited the doxorubicin-induced uPA expression in both RC-K8 and H69 cells. However, U0126 rather enhanced the doxorubicin-induced activation of caspase-3 and poly ADP-ribose polymerase (PARP), and U0126 itself activated caspase-3 and PARP. Interestingly, JNKI-1 inhibited the doxorubicin-induced activation of caspase-3 and PARP. Therefore, doxorubicin treatment activates the above three kinases, but different MAP kinase signaling is responsible in the doxorubicin-induced caspase activation and expression of uPA. Thus, we could possibly manipulate the direction of doxorubicin-induced MAP kinase activation and the effects of doxorubicin on the tumor cell biology by the use of MAP kinase inhibitors.

Original languageEnglish
Pages (from-to)310-319
Number of pages10
JournalOncology
Volume67
Issue number3-4
DOIs
Publication statusPublished - 2004

Fingerprint

Small Cell Lung Carcinoma
Urokinase-Type Plasminogen Activator
p38 Mitogen-Activated Protein Kinases
Doxorubicin
Lymphoma
Mitogen-Activated Protein Kinases
Poly(ADP-ribose) Polymerases
Caspase 3
JNK Mitogen-Activated Protein Kinases
Heat-Shock Proteins
Protein Kinases
Phosphotransferases
MAP Kinase Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Protein Kinase Inhibitors
Caspases
Cell Biology
Reactive Oxygen Species

Keywords

  • Apoptosis
  • Caspase
  • Doxorubicin
  • Human lymphoma cells
  • Mitogen-activated protein (MAP) kinase
  • Small cell lung carcinoma (SCLC) cells
  • Urokinase-type plasminogen activator (uPA)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Involvement of ERK1/2 and p38 MAP kinase in doxorubicin-induced uPA expression in human RC-K8 lymphoma and NCI-H69 small cell lung carcinoma cells. / Niiya, Masami; Niiya, Kenji; Shibakura, Misako; Asaumi, Noboru; Yoshida, Chikamasa; Shinagawa, Katsuji; Teshima, Takanori; Ishimaru, Fumihiko; Ikeda, Kazuma; Tanimoto, Mitsune.

In: Oncology, Vol. 67, No. 3-4, 2004, p. 310-319.

Research output: Contribution to journalArticle

Niiya, M, Niiya, K, Shibakura, M, Asaumi, N, Yoshida, C, Shinagawa, K, Teshima, T, Ishimaru, F, Ikeda, K & Tanimoto, M 2004, 'Involvement of ERK1/2 and p38 MAP kinase in doxorubicin-induced uPA expression in human RC-K8 lymphoma and NCI-H69 small cell lung carcinoma cells', Oncology, vol. 67, no. 3-4, pp. 310-319. https://doi.org/10.1159/000081332
Niiya, Masami ; Niiya, Kenji ; Shibakura, Misako ; Asaumi, Noboru ; Yoshida, Chikamasa ; Shinagawa, Katsuji ; Teshima, Takanori ; Ishimaru, Fumihiko ; Ikeda, Kazuma ; Tanimoto, Mitsune. / Involvement of ERK1/2 and p38 MAP kinase in doxorubicin-induced uPA expression in human RC-K8 lymphoma and NCI-H69 small cell lung carcinoma cells. In: Oncology. 2004 ; Vol. 67, No. 3-4. pp. 310-319.
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abstract = "We previously demonstrated the doxorubicin-induced urokinase-type plasminogen activator (uPA) expression in human RC-K8 lymphoma cells and NCI-H69 small cell lung carcinoma cells in which reactive oxygen species might be involved. Western blotting analysis revealed phosphorylation/activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase and stress-activated protein kinase/c-jun N-terminal protein kinase (SAPK/JNK) in doxorubicin-treated RC-K8 and H69 cells, and, therefore, we attempted to identify the MAP kinases implicated in doxorubicin-induced uPA expression by the use of their specific inhibitors. U0126, SB202190 and JNKI-1, inhibitors for MAPK kinase, (MEK) 1/2, p38 MAP kinase and SAPK/JNK, respectively, specifically and clearly inhibited their corresponding kinases. U0126 and SB202190, but not JNKI-1, almost completely inhibited the doxorubicin-induced uPA expression in both RC-K8 and H69 cells. However, U0126 rather enhanced the doxorubicin-induced activation of caspase-3 and poly ADP-ribose polymerase (PARP), and U0126 itself activated caspase-3 and PARP. Interestingly, JNKI-1 inhibited the doxorubicin-induced activation of caspase-3 and PARP. Therefore, doxorubicin treatment activates the above three kinases, but different MAP kinase signaling is responsible in the doxorubicin-induced caspase activation and expression of uPA. Thus, we could possibly manipulate the direction of doxorubicin-induced MAP kinase activation and the effects of doxorubicin on the tumor cell biology by the use of MAP kinase inhibitors.",
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AU - Niiya, Kenji

AU - Shibakura, Misako

AU - Asaumi, Noboru

AU - Yoshida, Chikamasa

AU - Shinagawa, Katsuji

AU - Teshima, Takanori

AU - Ishimaru, Fumihiko

AU - Ikeda, Kazuma

AU - Tanimoto, Mitsune

PY - 2004

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AB - We previously demonstrated the doxorubicin-induced urokinase-type plasminogen activator (uPA) expression in human RC-K8 lymphoma cells and NCI-H69 small cell lung carcinoma cells in which reactive oxygen species might be involved. Western blotting analysis revealed phosphorylation/activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase and stress-activated protein kinase/c-jun N-terminal protein kinase (SAPK/JNK) in doxorubicin-treated RC-K8 and H69 cells, and, therefore, we attempted to identify the MAP kinases implicated in doxorubicin-induced uPA expression by the use of their specific inhibitors. U0126, SB202190 and JNKI-1, inhibitors for MAPK kinase, (MEK) 1/2, p38 MAP kinase and SAPK/JNK, respectively, specifically and clearly inhibited their corresponding kinases. U0126 and SB202190, but not JNKI-1, almost completely inhibited the doxorubicin-induced uPA expression in both RC-K8 and H69 cells. However, U0126 rather enhanced the doxorubicin-induced activation of caspase-3 and poly ADP-ribose polymerase (PARP), and U0126 itself activated caspase-3 and PARP. Interestingly, JNKI-1 inhibited the doxorubicin-induced activation of caspase-3 and PARP. Therefore, doxorubicin treatment activates the above three kinases, but different MAP kinase signaling is responsible in the doxorubicin-induced caspase activation and expression of uPA. Thus, we could possibly manipulate the direction of doxorubicin-induced MAP kinase activation and the effects of doxorubicin on the tumor cell biology by the use of MAP kinase inhibitors.

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KW - Small cell lung carcinoma (SCLC) cells

KW - Urokinase-type plasminogen activator (uPA)

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