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Article Open Access

Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma

  • Authors:
    • Xingyang Zhu
    • Xiaoling Song
    • Kun Xie
    • Xue Zhang
    • Wei He
    • Fubao Liu
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Affiliated Hospital of Medical University of Anhui, Hefei, Anhui 230022, P.R. China, Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200082, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1143-1151
    |
    Published online on: August 30, 2017
       https://doi.org/10.3892/ijmm.2017.3113
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Abstract

Osthole is a natural coumarin isolated from Umbelliferae plant monomers. Previous research has indicated that osthole exerts a wide variety of biological effects, acting as anti-seizure, anti-osteoporosis and anti-inflammation. However, the regulatory effect and related molecular mechanism of osthole in intrahepatic cholangiocarcinoma (ICC) remain unknown. In the present study, the authors found that osthole inhibited ICC cell lines in a dose- and time-dependent manner. Osthole also significantly induced mitochondrial-dependent apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9, and cleaved poly ADP-ribose polymerase expression, and by downregulating Bcl-2 expression. Moreover, the levels of p-Akt and PI3K were significantly decreased, while total Akt protein levels were unchanged. Following transfection with wild-type-Akt and constitutively active (CA)-Akt plasmids, the effects of osthole were decreased. Osthole was also able to suppress tumor growth in vivo. Together, these data demonstrated that osthole induces mitochondrial-dependent apoptosis via the PI3K/Akt pathway, suggesting that osthole may represent a novel and effective agent for the treatment of ICC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu X, Song X, Xie K, Zhang X, He W and Liu F: Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma. Int J Mol Med 40: 1143-1151, 2017.
APA
Zhu, X., Song, X., Xie, K., Zhang, X., He, W., & Liu, F. (2017). Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma. International Journal of Molecular Medicine, 40, 1143-1151. https://doi.org/10.3892/ijmm.2017.3113
MLA
Zhu, X., Song, X., Xie, K., Zhang, X., He, W., Liu, F."Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma". International Journal of Molecular Medicine 40.4 (2017): 1143-1151.
Chicago
Zhu, X., Song, X., Xie, K., Zhang, X., He, W., Liu, F."Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma". International Journal of Molecular Medicine 40, no. 4 (2017): 1143-1151. https://doi.org/10.3892/ijmm.2017.3113
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu X, Song X, Xie K, Zhang X, He W and Liu F: Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma. Int J Mol Med 40: 1143-1151, 2017.
APA
Zhu, X., Song, X., Xie, K., Zhang, X., He, W., & Liu, F. (2017). Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma. International Journal of Molecular Medicine, 40, 1143-1151. https://doi.org/10.3892/ijmm.2017.3113
MLA
Zhu, X., Song, X., Xie, K., Zhang, X., He, W., Liu, F."Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma". International Journal of Molecular Medicine 40.4 (2017): 1143-1151.
Chicago
Zhu, X., Song, X., Xie, K., Zhang, X., He, W., Liu, F."Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma". International Journal of Molecular Medicine 40, no. 4 (2017): 1143-1151. https://doi.org/10.3892/ijmm.2017.3113
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