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Cited 16 time in webofscience Cited 18 time in scopus
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Antitumorigenic effect of plumbagin by induction of SH2-containing protein tyrosine phosphatase 1 in human gastric cancer cells

Authors
Joo, Moon KyungPark, Jong-JaeKim, Sung HoYoo, Hy SoonLee, Beom JaeChun, Hoon JaiLee, Sang WooBak, Young-Tae
Issue Date
Jun-2015
Publisher
SPANDIDOS PUBL LTD
Keywords
plumbagin; Janus kinase 2; signal transducer and activator of transcription 3; SH2-containing protein tyrosine phosphatase 1
Citation
INTERNATIONAL JOURNAL OF ONCOLOGY, v.46, no.6, pp.2380 - 2388
Indexed
SCIE
SCOPUS
Journal Title
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume
46
Number
6
Start Page
2380
End Page
2388
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/7849
DOI
10.3892/ijo.2015.2935
ISSN
1019-6439
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.
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Joo, Moon Kyung
Guro Hospital (Department of Gastroenterology and Hepatology, Guro Hospital)
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