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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 268468, 12 pages
Research Article

β-Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells

Department of Traditional Chinese Medicine, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China

Received 24 January 2013; Revised 15 March 2013; Accepted 23 March 2013

Academic Editor: Yu-Jen Chen

Copyright © 2013 Bing Yan 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.


Emerging evidence suggests that cancer stem cells are involved in tumor angiogenesis. The Notch signaling pathway is one of the most important regulators of these processes. β-Elemene, a naturally occurring compound extracted from Curcumae Radix, has been used as an antitumor drug for various cancers in China. However, its underlying mechanism in the treatment of gastric cancer remains largely unknown. Here, we report that CD44+ gastric cancer stem-like cells (GCSCs) showed enhanced proliferation capacity compared to their CD44− counterparts, and this proliferation was accompanied by the high expression of Notch-1 (in vitro). These cells were also more superior in spheroid colony formation (in vitro) and tumorigenicity (in vivo) and positively associated with microvessel density (in vivo). β-Elemene was demonstrated to effectively inhibit the viability of GCSCs in a dose-dependent manner, most likely by suppressing Notch-1 (in vitro). β-Elemene also contributed to growth suppression and attenuated the angiogenesis capacity of these cells (in vivo) most likely by interfering with the expression of Notch-1 but not with Dll4. Our findings indicated that GCSCs play an important role in tumor angiogenesis, and Notch-1 is one of the most likely mediators involved in these processes. β-Elemene was effective at attenuating angiogenesis by targeting the GCSCs, which could be regarded as a potential mechanism for its efficacy in gastric cancer management in the future.