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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 518301, 12 pages
http://dx.doi.org/10.1155/2013/518301
Research Article

Potential Therapeutic Role of Hispidulin in Gastric Cancer through Induction of Apoptosis via NAG-1 Signaling

1Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Ilan 260, Taiwan
2Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
3Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
4Department of Electrical Engineering, National Central University, Jhongli 32001, Taiwan
5Division of General Surgery, Department of Surgery, Tri-Service General Hospital, Taipei 114, Taiwan

Received 12 March 2013; Revised 7 June 2013; Accepted 9 June 2013

Academic Editor: Thomas Efferth

Copyright © 2013 Chao Yuan Yu 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

Gastric cancer is one of the most common malignant cancers due to poor prognoses and high mortality rates worldwide. However, an effective chemotherapeutic drug without side effects remains lacking. Saussurea involucrata (SI) Kar. et Kir., also known as snow lotus, grows in mountainous rocky habitats at 2600 m elevation in the Tian Shan and A’er Tai regions of China. The ethyl acetate extract of SI had been shown to inhibit proliferation and induce apoptosis in various tumor cells. In this study, we demonstrated that Hispidulin, active ingredients in SI, inhibits the growth of AGS gastric cancer cells. After Hispidulin treatment, NAG-1 remained highly expressed, whereas COX-2 expression was downregulated. Flow cytometric analysis indicated that Hispidulin induces G1/S phase arrest and apoptosis in time- and concentration-dependent manners. G1/S arrest correlated with upregulated p21/WAF1 and p16 and downregulated cyclin D1 and cyclin E, independent of p53 pathway. In addition, Hispidulin can elevate Egr-1 expression and ERK1/2 activity, whereas ERK1/2 inhibitor markedly attenuated NAG-1 mediated apoptosis. Taken together, Hispidulin can efficiently activate ERK1/2 signaling followed by NAG-1 constitutive expression and trigger cell cycle arrest as well as apoptosis in cancer cell. It can be a potential compound for combination therapy of gastric cancer in the future.