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A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells

Oncogene volume 24, pages 2114–2120 (2005)Cite this article

Abstract

Prostate cancer is the second highest cause of cancer-related deaths of men in the US. Signal transducers and activators of transcription (STATs) proteins are a small family of latent cytoplasmic transcription factors that act downstream of Janus kinase (JAK) activation and mediate intracellular signaling from a wide variety of cytokines, growth factors, and hormones. Aberrant activation of STAT3 has been implicated in the progression of many human carcinomas, including prostate cancer. Previously, we have characterized a novel tyrosine kinase inhibitor peptide, Tkip, that is a mimetic of suppressor of cytokine signaling 1 (SOCS-1). Similar to SOCS-1, Tkip binds to the autophosphorylation site of JAK2 and inhibits phosphorylation of STAT1α. In this study, we determined the inhibitory effects of Tkip on the human prostate cancer cell lines DU145 and LNCaP. Tkip inhibited cellular proliferation of both DU145 and LNCaP cells, with a slightly greater antiproliferative effect on DU145 cells. Cell cycle analysis using flow cytometry showed Tkip blockage of progression into the S phase of the cell cycle. Tkip also inhibited constitutive (DU145) and IL-6-induced (LNCaP) activation of STAT3, consistent with the fact that STAT3 activation is mediated by JAK2. Tkip also slightly reduced the levels of cyclin D1, an important regulator of cell cycle progression into S phase, in DU145 and LNCaP cancer cell lines. These data describe a potentially important therapeutic that targets both constitutive and IL-6-induced STAT3 activation in human prostate cancer cell lines.

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Acknowledgements

This work was supported by Grant AI56152 (to HMJ) from the National Institutes of Health and by the UNCF-Merck Graduate Science Research Dissertation Fellowship (to LOF). This manuscript is Florida Experiment Station Journal Series No. R-10648.

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  1. Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, 32611, USA

    Lawrence O Flowers & Howard M Johnson

  2. Scripps Research Institute, Biomedical Science Center, FAU, 777 Glades Road, Boca Raton, FL, 33431, USA

    Prem S Subramaniam

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  1. Lawrence O Flowers
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Correspondence to Howard M Johnson.

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Flowers, L., Subramaniam, P. & Johnson, H. A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells. Oncogene 24, 2114–2120 (2005). https://doi.org/10.1038/sj.onc.1208437

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