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

  • Authors:
    • Moon Kyung Joo
    • Jong‑Jae Park
    • Sung Ho Kim
    • Hyo Soon Yoo
    • Beom Jae Lee
    • Hoon Jai Chun
    • Sang Woo Lee
    • Young‑Tae Bak
  • View Affiliations

  • Published online on: March 26, 2015     https://doi.org/10.3892/ijo.2015.2935
  • Pages: 2380-2388
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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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June-2015
Volume 46 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Joo MK, Park JJ, Kim SH, Yoo HS, Lee BJ, Chun HJ, Lee SW and Bak YT: Antitumorigenic effect of plumbagin by induction of SH2‑containing protein tyrosine phosphatase 1 in human gastric cancer cells. Int J Oncol 46: 2380-2388, 2015
APA
Joo, M.K., Park, J., Kim, S.H., Yoo, H.S., Lee, B.J., Chun, H.J. ... Bak, Y. (2015). Antitumorigenic effect of plumbagin by induction of SH2‑containing protein tyrosine phosphatase 1 in human gastric cancer cells. International Journal of Oncology, 46, 2380-2388. https://doi.org/10.3892/ijo.2015.2935
MLA
Joo, M. K., Park, J., Kim, S. H., Yoo, H. S., Lee, B. J., Chun, H. J., Lee, S. W., Bak, Y."Antitumorigenic effect of plumbagin by induction of SH2‑containing protein tyrosine phosphatase 1 in human gastric cancer cells". International Journal of Oncology 46.6 (2015): 2380-2388.
Chicago
Joo, M. K., Park, J., Kim, S. H., Yoo, H. S., Lee, B. J., Chun, H. J., Lee, S. W., Bak, Y."Antitumorigenic effect of plumbagin by induction of SH2‑containing protein tyrosine phosphatase 1 in human gastric cancer cells". International Journal of Oncology 46, no. 6 (2015): 2380-2388. https://doi.org/10.3892/ijo.2015.2935