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

  • Published online on: August 30, 2017     https://doi.org/10.3892/ijmm.2017.3113
  • Pages: 1143-1151
  • Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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October-2017
Volume 40 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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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