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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 745295, 14 pages
Research Article

Saikosaponin-d Enhances the Anticancer Potency of TNF- via Overcoming Its Undesirable Response of Activating NF-Kappa B Signalling in Cancer Cells

1State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China
2Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Hong Kong
3Department of Biology, Hong Kong Baptist University, Hong Kong

Received 8 January 2013; Accepted 7 February 2013

Academic Editor: Shuang-En Chuang

Copyright © 2013 Vincent Kam Wai Wong 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.


Tumor necrosis factor-alpha (TNF-α) was reported as anticancer therapy due to its cytotoxic effect against an array of tumor cells. However, its undesirable responses of TNF-α on activating NF-κB signaling and pro-metastatic property limit its clinical application in treating cancers. Therefore, sensitizing agents capable of overcoming this undesirable effect must be valuable for facilitating the usage of TNF-α-mediated apoptosis therapy for cancer patients. Previously, saikosaponin-d (Ssd), a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae), showed to exhibit a variety of pharmacological activities such as antiinflammation, antibacteria, antivirus and anticancer. Recently, we found that Ssd could inhibit the activated T lymphocytes via suppression of NF-κB, NF-AT and AP-1 signaling. Here, we showed that Ssd significantly potentiated TNF-α-mediated cell death in HeLa and HepG2 cancer cells via suppression of TNF-α-induced NF-κB activation and its target genes expression involving cancer cell proliferation, invasion, angiogenesis and survival. Also, Ssd revealed a significant potency of abolishing TNF-α-induced cancer cell invasion and angiogenesis in HUVECs while inducing apoptosis via enhancing the loss of mitochondrial membrane potential in HeLa cells. Collectively, these findings indicate that Ssd has a significant potential to be developed as a combined adjuvant remedy with TNF-α for cancer patients.