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Article

Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells

  • Authors:
    • Gi Dae Kim
    • Jedo Oh
    • Hyen-Joo Park
    • Kihwan Bae
    • Sang Kook Lee
  • View Affiliations / Copyright

    Affiliations: Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea, College of Pharmacy, Chungnam National University, Daejon, Republic of Korea
  • Pages: 600-610
    |
    Published online on: May 24, 2013
       https://doi.org/10.3892/ijo.2013.1959
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Abstract

Magnolol, a neolignan from the traditional medicinal plant Magnolia obovata, has been shown to possess neuroprotective, anti-inflammatory, anticancer and anti-angiogenic activities. However, the precise mechanism of the anti-angiogenic activity of magnolol remains to be elucidated. In the present study, the anti-angiogenic effect of magnolol was evaluated in mouse embryonic stem (mES)/embryoid body (EB)-derived endothelial-like cells. The endothelial-like cells were obtained by differentiation from mES/EB cells. Magnolol (20 µM) significantly suppressed the transcriptional and translational expression of platelet endothelial cell adhesion molecule (PECAM), an endothelial biomarker, in mES/EB-derived endothelial-like cells. To further understand the molecular mechanism of the suppression of PECAM expression, signaling pathways were analyzed in the mES/EB-derived endothelial-like cells. Magnolol induced the generation of reactive oxygen species (ROS) by mitochondria, a process that was associated with the induction of apoptosis as determined by positive Annexin V staining and the activation of cleaved caspase-3. The involvement of ROS generation by magnolol was confirmed by treatment with an antioxidant, N-acetyl-cysteine (NAC). NAC inhibited the magnolol-mediated induction of ROS generation and suppression of PECAM expression. In addition, magnolol suppressed the activation of MAPKs (ERK, JNK and p38) and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Taken together, these findings demonstrate for the first time that the anti-angiogenic activity of magnolol may be associated with ROS-mediated apoptosis and the suppression of the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells.
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Copy and paste a formatted citation
Spandidos Publications style
Kim GD, Oh J, Park H, Bae K and Lee SK: Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Int J Oncol 43: 600-610, 2013.
APA
Kim, G.D., Oh, J., Park, H., Bae, K., & Lee, S.K. (2013). Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. International Journal of Oncology, 43, 600-610. https://doi.org/10.3892/ijo.2013.1959
MLA
Kim, G. D., Oh, J., Park, H., Bae, K., Lee, S. K."Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells". International Journal of Oncology 43.2 (2013): 600-610.
Chicago
Kim, G. D., Oh, J., Park, H., Bae, K., Lee, S. K."Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells". International Journal of Oncology 43, no. 2 (2013): 600-610. https://doi.org/10.3892/ijo.2013.1959
Copy and paste a formatted citation
x
Spandidos Publications style
Kim GD, Oh J, Park H, Bae K and Lee SK: Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Int J Oncol 43: 600-610, 2013.
APA
Kim, G.D., Oh, J., Park, H., Bae, K., & Lee, S.K. (2013). Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. International Journal of Oncology, 43, 600-610. https://doi.org/10.3892/ijo.2013.1959
MLA
Kim, G. D., Oh, J., Park, H., Bae, K., Lee, S. K."Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells". International Journal of Oncology 43.2 (2013): 600-610.
Chicago
Kim, G. D., Oh, J., Park, H., Bae, K., Lee, S. K."Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells". International Journal of Oncology 43, no. 2 (2013): 600-610. https://doi.org/10.3892/ijo.2013.1959
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