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Article

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

  • Authors:
    • Ji‑An Zhao
    • Mei‑Xiang Sang
    • Cui‑Zhi Geng
    • Shi‑Jie Wang
    • Bao‑En Shan
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050013, P.R. China, Tumor Research Institute, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
  • Pages: 4252-4262
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    Published online on: September 13, 2016
       https://doi.org/10.3892/ol.2016.5126
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Abstract

Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to prevent tumor development in cancer; however, the clinical application of CUR is limited by its instability and poor metabolic properties. The present study offers an strategy for a novel CUR analogue, (1E,4E)‑1,5‑bis(2‑bromophenyl)penta‑1,4‑dien‑3‑one (GL63), to be used as a potential therapeutic agent for hepatocellular carcinoma (HCC) in vitro and in vivo. The current study demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK‑HEP‑1 cells in a dose‑dependent manner, and was more potent than CUR, according to the flow cytometry data. The present study demonstrated for the first time that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective effect against HCC cell growth. GL63 was more effective than CUR in regulating STAT3 downstream targets, which contributed to the suppression of cell proliferation and the induction of cell apoptosis. In addition, the effects of GL63 were tested in a model of N‑nitrosodiethylamine (DEN)‑induced HCC in Wistar rats. Although macroscopic and microscopic features suggested that both GL63 and CUR were effective in inhibiting DEN‑induced hepatocarcinogenesis, GL63 exerted a stronger effect than CUR. Immunohistochemical analysis for proliferating cell nuclear antigen demonstrated significant differences among the DEN‑bearing non‑treated, DEN‑bearing GL63‑treated and DEN‑bearing, CUR‑treated groups (P=0.039). It was concluded that GL63 was a potent agent able to suppress the proliferation of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more favorable pharmacological activity than CUR, and may be a more potent compound for the prevention of DEN‑induced hepatocarcinogenesis in rats than CUR.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao JA, Sang MX, Geng CZ, Wang SJ and Shan BE: A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma. Oncol Lett 12: 4252-4262, 2016.
APA
Zhao, J., Sang, M., Geng, C., Wang, S., & Shan, B. (2016). A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma. Oncology Letters, 12, 4252-4262. https://doi.org/10.3892/ol.2016.5126
MLA
Zhao, J., Sang, M., Geng, C., Wang, S., Shan, B."A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma". Oncology Letters 12.5 (2016): 4252-4262.
Chicago
Zhao, J., Sang, M., Geng, C., Wang, S., Shan, B."A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma". Oncology Letters 12, no. 5 (2016): 4252-4262. https://doi.org/10.3892/ol.2016.5126
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao JA, Sang MX, Geng CZ, Wang SJ and Shan BE: A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma. Oncol Lett 12: 4252-4262, 2016.
APA
Zhao, J., Sang, M., Geng, C., Wang, S., & Shan, B. (2016). A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma. Oncology Letters, 12, 4252-4262. https://doi.org/10.3892/ol.2016.5126
MLA
Zhao, J., Sang, M., Geng, C., Wang, S., Shan, B."A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma". Oncology Letters 12.5 (2016): 4252-4262.
Chicago
Zhao, J., Sang, M., Geng, C., Wang, S., Shan, B."A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma". Oncology Letters 12, no. 5 (2016): 4252-4262. https://doi.org/10.3892/ol.2016.5126
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