Abstract
The anoikis-sensitization activity of imperatorin, an active furanocoumarin component of Angelica dahurica root, is reported herein for the first time. The present study demonstrated that the imperatorin treatment at sub-toxic concentrations enhanced human lung cancer H23 cell apoptosis after detachment. A Western blot analysis showed that imperatorin significantly enhanced the p53 protein level, which subsequently down-regulated Mcl-1 protein and up-regulated Bax, while it had a minimal effect on Bcl-2 expression. In addition, an anchorage-independent growth assay was performed to support the anti-metastasis potential of imperatorin. Consistent with anoikis assay, imperatorin exhibited a strong inhibitory effect on the anchorage-independent growth of the cells. Further, this study demonstrated that imperatorin sensitizes anoikis in other lung cancer cells, namely, H292 and A549. Because anoikis was shown to be a critical hindrance in preventing cancer cell metastasis, the knowledge regarding such an activity and an underlying mechanism may lead to the development of this compound for a cancer therapy.
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Acknowledgments
This research was supported by the Thailand Research Fund (to P. Chanvorachote) and the 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund). The authors wish to thank Mr. Krich Rajprasit (Srinakharinwirot University) for proofreading the manuscript.
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Choochuay, K., Chunhacha, P., Pongrakhananon, V. et al. Imperatorin sensitizes anoikis and inhibits anchorage-independent growth of lung cancer cells. J Nat Med 67, 599–606 (2013). https://doi.org/10.1007/s11418-012-0719-y
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DOI: https://doi.org/10.1007/s11418-012-0719-y