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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 809204, 11 pages
http://dx.doi.org/10.1155/2012/809204
Research Article

Potential Therapeutic Role of Z-Isochaihulactone in Lung Cancer through Induction of Apoptosis via Notch Signaling

1Department of Dentistry, Hualien Armed Forces General Hospital, Hualien 97144, Taiwan
2Laboratory of Exercise Biochemistry, Taipei Sports University, Taipei 11106, Taiwan
3NTU Center for Genomic Medicine, National Taiwan University, Taipei 10055, Taiwan
4Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 10055, Taiwan
5Department of Biotechnology and Animal Science, National Ilan University, Ilan 26041, Taiwan
6Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Received 20 June 2012; Accepted 12 August 2012

Academic Editor: Andreas Sandner-Kiesling

Copyright © 2012 Jie-Ping Ou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Lung cancer is one of the leading causes of cancer death in worldwide and required for novel therapeutic strategy. Our previous research demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (BS-AE) and its component isochaihulactone induce antiproliferative and apoptotic effects on the lung adenocarcinoma cell line. Structural analysis has identified isochaihulactone as a lignan, with a chiral center and two racemic forms (Z-isochaihulactone and E-isochaihulactone). In this study, Z-isochaihulactone displayed significantly higher tumor cytotoxicity than E-isochaihulactone in A549 cells. The notch signaling pathway plays a pivotal role in determination of cell fate during development, while in lung cancer, it might have oncogenic or tumor-suppressive controversial functions. We showed that Z-isochaihulactone induced morphological changes in the A549 cells, inhibited cell growth, and arrested the cell cycle at the G2/M phase. It also induced upregulation of the active form of Notch1 (notch intracellular domain, NICD), which further induced p21 and c-Myc expression in time- and dose-dependent manners. Administrations of Z-isochaihulactone in nude mice can significantly inhibit tumor growth due to enhancement of NICD expression confirmed by immunohistochemical analysis. Taken together, our results supported that Z-isochaihulactone can efficiently inhibit tumorigenicity and be a potential compound for therapy.