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Article

GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway

  • Authors:
    • Sen Lu
    • Yun Gao
    • Xinli Huang
    • Xuehao Wang
  • View Affiliations / Copyright

    Affiliations: Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing 210029, P.R. China
  • Pages: 1259-1267
    |
    Published online on: February 14, 2014
       https://doi.org/10.3892/ijo.2014.2305
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Abstract

GYY4137, a hydrogen sulfide (H2S) donor, exhibits anticancer activity by a combination of cell cycle arrest and promoting apoptosis, and inhibits tumor growth, however, the precise mechanisms involved remain unclear. In this study, we discovered that GYY4137-mediated suppression of cell proliferation in human hepatocellular carcinoma (HCC) cell lines and tumor growth in a subcutaneous HepG2 xenograft model may be due to directly targeting the signal transducer and activator of transcription 3 (STAT3) pathway. We found that GYY4137 suppressed STAT3 activation by reducing p-STAT3 (Y705) levels effectively in HepG2 and Bel7402 cells. Altered expression levels of STAT3-regulated downstream proteins including Bcl-2, cyclin D1, Mcl-1, survivin, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) may contribute to the inhibition of G1/S cell cycle transition and angiogenesis. Increased cleaved caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage may induce cell apoptosis in HepG2 and Bel7402 cells. In vivo, GYY4137 significantly inhibited tumor growth in the subcutaneous HepG2 xenograft model by inhibiting STAT3 activation and its target gene expression. These results suggest that GYY4137-mediated suppression of HCC growth may be due to the inhibition of the STAT3 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Lu S, Gao Y, Huang X and Wang X: GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. Int J Oncol 44: 1259-1267, 2014.
APA
Lu, S., Gao, Y., Huang, X., & Wang, X. (2014). GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. International Journal of Oncology, 44, 1259-1267. https://doi.org/10.3892/ijo.2014.2305
MLA
Lu, S., Gao, Y., Huang, X., Wang, X."GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway". International Journal of Oncology 44.4 (2014): 1259-1267.
Chicago
Lu, S., Gao, Y., Huang, X., Wang, X."GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway". International Journal of Oncology 44, no. 4 (2014): 1259-1267. https://doi.org/10.3892/ijo.2014.2305
Copy and paste a formatted citation
x
Spandidos Publications style
Lu S, Gao Y, Huang X and Wang X: GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. Int J Oncol 44: 1259-1267, 2014.
APA
Lu, S., Gao, Y., Huang, X., & Wang, X. (2014). GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. International Journal of Oncology, 44, 1259-1267. https://doi.org/10.3892/ijo.2014.2305
MLA
Lu, S., Gao, Y., Huang, X., Wang, X."GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway". International Journal of Oncology 44.4 (2014): 1259-1267.
Chicago
Lu, S., Gao, Y., Huang, X., Wang, X."GYY4137, a hydrogen sulfide (H2S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway". International Journal of Oncology 44, no. 4 (2014): 1259-1267. https://doi.org/10.3892/ijo.2014.2305
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