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 language | English |
|---|---|
| Pages (from-to) | 2380-2388 |
| Number of pages | 9 |
| Journal | International Journal of Oncology |
| Volume | 46 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2015 Jun 1 |
Fingerprint
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
Antitumorigenic effect of plumbagin by induction of SH2-containing protein tyrosine phosphatase 1 in human gastric cancer cells. / Joo, Moon Kyung; Park, Jong Jae; Kim, Sung Ho; Yoo, Hyo Soon; Lee, Beomjae; Chun, Hoon-Jai; Lee, Sang Woo; Bak, Young-Tae.
In: International Journal of Oncology, Vol. 46, No. 6, 01.06.2015, p. 2380-2388.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84928560787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928560787&partnerID=8YFLogxK
U2 - 10.3892/ijo.2015.2935
DO - 10.3892/ijo.2015.2935
M3 - Article
C2 - 25815436
AN - SCOPUS:84928560787
VL - 46
SP - 2380
EP - 2388
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 6
ER -