Antitumorigenic effect of plumbagin by induction of SH2-containing protein tyrosine phosphatase 1 in human gastric cancer cells

Moon Kyung Joo, Jong Jae Park, Sung Ho Kim, Hyo Soon Yoo, Beomjae Lee, Hoon-Jai Chun, Sang Woo Lee, Young-Tae Bak

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12 Citations (Scopus)

Abstract

A recent study reported that plumbagin downregulated the activity of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various antitumor effects in multiple myeloma cells. We aimed in this in vitro study to demonstrate the inhibition of JAK2/STAT3 pathway by plumbagin through inducing SH2-containing protein tyrosine phosphatase 1 (SHP1) expression in the MKN-28 gastric cancer cell line. We performed western blot analysis to measure SHP1, phospho-JAK2/STAT3 level, and observed that plumbagin induced SHP1 expression and simultaneously downregulated phospho-JAK2/STAT3 in MKN-28 cells, with negative SHP1 expression. This effect was consistent when JAK2/STAT3 signaling was activated by interleukin-6 (IL-6), and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, vascular endothelial growth factor (VEGF)-1, Bcl-xL, survivin and matrix metalloproteinase-9 (MMP-9), known target products of STAT3 activation in gastric cancinogenesis by reverse transcription-polymerase chain reaction (RT-PCR). Several functional studies such as water soluble tetrazolium salt-1 (WST-1) assay, wound closure assay, Matrigel invasion assay and Annexin V assay were also performed, and we validated the functional effect of plumbagin for inhibition of cell proliferation, migration and invasion, and induction of apoptosis. Collectively, our findings suggest that plumbagin is a potential regulator of cellular growth, migration, invasion and apoptosis by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.

Original languageEnglish
Pages (from-to)2380-2388
Number of pages9
JournalInternational Journal of Oncology
Volume46
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

Fingerprint

Protein Phosphatase 1
STAT3 Transcription Factor
Protein Tyrosine Phosphatases
Janus Kinase 2
Stomach Neoplasms
Down-Regulation
Tetrazolium Salts
Apoptosis
Annexin A5
Phosphoprotein Phosphatases
Cyclin D1
Matrix Metalloproteinase 9
plumbagin
Multiple Myeloma
Vascular Endothelial Growth Factor A
Transcriptional Activation
Reverse Transcription
Cell Movement
Interleukin-6
Stomach

Keywords

  • Janus kinase 2
  • Plumbagin
  • SH2-containing protein tyrosine phosphatase 1
  • Signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{d5e39cc5218f44eeace49b32065ea08b,
title = "Antitumorigenic effect of plumbagin by induction of SH2-containing protein tyrosine phosphatase 1 in human gastric cancer cells",
abstract = "A recent study reported that plumbagin downregulated the activity of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various antitumor effects in multiple myeloma cells. We aimed in this in vitro study to demonstrate the inhibition of JAK2/STAT3 pathway by plumbagin through inducing SH2-containing protein tyrosine phosphatase 1 (SHP1) expression in the MKN-28 gastric cancer cell line. We performed western blot analysis to measure SHP1, phospho-JAK2/STAT3 level, and observed that plumbagin induced SHP1 expression and simultaneously downregulated phospho-JAK2/STAT3 in MKN-28 cells, with negative SHP1 expression. This effect was consistent when JAK2/STAT3 signaling was activated by interleukin-6 (IL-6), and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, vascular endothelial growth factor (VEGF)-1, Bcl-xL, survivin and matrix metalloproteinase-9 (MMP-9), known target products of STAT3 activation in gastric cancinogenesis by reverse transcription-polymerase chain reaction (RT-PCR). Several functional studies such as water soluble tetrazolium salt-1 (WST-1) assay, wound closure assay, Matrigel invasion assay and Annexin V assay were also performed, and we validated the functional effect of plumbagin for inhibition of cell proliferation, migration and invasion, and induction of apoptosis. Collectively, our findings suggest that plumbagin is a potential regulator of cellular growth, migration, invasion and apoptosis by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.",
keywords = "Janus kinase 2, Plumbagin, SH2-containing protein tyrosine phosphatase 1, Signal transducer and activator of transcription 3",
author = "Joo, {Moon Kyung} and Park, {Jong Jae} and Kim, {Sung Ho} and Yoo, {Hyo Soon} and Beomjae Lee and Hoon-Jai Chun and Lee, {Sang Woo} and Young-Tae Bak",
year = "2015",
month = "6",
day = "1",
doi = "10.3892/ijo.2015.2935",
language = "English",
volume = "46",
pages = "2380--2388",
journal = "International Journal of Oncology",
issn = "1019-6439",
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TY - JOUR

T1 - Antitumorigenic effect of plumbagin by induction of SH2-containing protein tyrosine phosphatase 1 in human gastric cancer cells

AU - Joo, Moon Kyung

AU - Park, Jong Jae

AU - Kim, Sung Ho

AU - Yoo, Hyo Soon

AU - Lee, Beomjae

AU - Chun, Hoon-Jai

AU - Lee, Sang Woo

AU - Bak, Young-Tae

PY - 2015/6/1

Y1 - 2015/6/1

N2 - A recent study reported that plumbagin downregulated the activity of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various antitumor effects in multiple myeloma cells. We aimed in this in vitro study to demonstrate the inhibition of JAK2/STAT3 pathway by plumbagin through inducing SH2-containing protein tyrosine phosphatase 1 (SHP1) expression in the MKN-28 gastric cancer cell line. We performed western blot analysis to measure SHP1, phospho-JAK2/STAT3 level, and observed that plumbagin induced SHP1 expression and simultaneously downregulated phospho-JAK2/STAT3 in MKN-28 cells, with negative SHP1 expression. This effect was consistent when JAK2/STAT3 signaling was activated by interleukin-6 (IL-6), and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, vascular endothelial growth factor (VEGF)-1, Bcl-xL, survivin and matrix metalloproteinase-9 (MMP-9), known target products of STAT3 activation in gastric cancinogenesis by reverse transcription-polymerase chain reaction (RT-PCR). Several functional studies such as water soluble tetrazolium salt-1 (WST-1) assay, wound closure assay, Matrigel invasion assay and Annexin V assay were also performed, and we validated the functional effect of plumbagin for inhibition of cell proliferation, migration and invasion, and induction of apoptosis. Collectively, our findings suggest that plumbagin is a potential regulator of cellular growth, migration, invasion and apoptosis by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.

AB - A recent study reported that plumbagin downregulated the activity of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various antitumor effects in multiple myeloma cells. We aimed in this in vitro study to demonstrate the inhibition of JAK2/STAT3 pathway by plumbagin through inducing SH2-containing protein tyrosine phosphatase 1 (SHP1) expression in the MKN-28 gastric cancer cell line. We performed western blot analysis to measure SHP1, phospho-JAK2/STAT3 level, and observed that plumbagin induced SHP1 expression and simultaneously downregulated phospho-JAK2/STAT3 in MKN-28 cells, with negative SHP1 expression. This effect was consistent when JAK2/STAT3 signaling was activated by interleukin-6 (IL-6), and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, vascular endothelial growth factor (VEGF)-1, Bcl-xL, survivin and matrix metalloproteinase-9 (MMP-9), known target products of STAT3 activation in gastric cancinogenesis by reverse transcription-polymerase chain reaction (RT-PCR). Several functional studies such as water soluble tetrazolium salt-1 (WST-1) assay, wound closure assay, Matrigel invasion assay and Annexin V assay were also performed, and we validated the functional effect of plumbagin for inhibition of cell proliferation, migration and invasion, and induction of apoptosis. Collectively, our findings suggest that plumbagin is a potential regulator of cellular growth, migration, invasion and apoptosis by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.

KW - Janus kinase 2

KW - Plumbagin

KW - SH2-containing protein tyrosine phosphatase 1

KW - Signal transducer and activator of transcription 3

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U2 - 10.3892/ijo.2015.2935

DO - 10.3892/ijo.2015.2935

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JO - International Journal of Oncology

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