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, phosphor-JAK2/STAT3 level, and observed that plumbagin induced SHP1 expression and simultaneously downregulated phosphor-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 carcinogenesis 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.
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152‑703, Republic of Korea.
authors: Moon Kyung
authors: MK
authors: Joo
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152‑703, Republic of Korea.
authors: Jong-Jae
authors: JJ
authors: Park
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152‑703, Republic of Korea.
authors: Sung Ho
authors: SH
authors: Kim
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152‑703, Republic of Korea.
authors: Hyo Soon
authors: HS
authors: Yoo
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152‑703, Republic of Korea.
authors: Beom Jae
authors: BJ
authors: Lee
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Anam Hospital, Seoul 136‑705, Republic of Korea.
authors: Hoon Jai
authors: HJ
authors: Chun
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Ansan Hospital, Ansan, Gyeonggi 425‑707, Republic of Korea.
authors: Sang Woo
authors: SW
authors: Lee
authors: Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul 152‑703, Republic of Korea.
authors: Young-Tae
authors: YT
authors: Bak
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C014758:plumbagin