title: Saikosaponin-d Enhances the Anticancer Potency of TNF-α via Overcoming Its Undesirable Response of Activating NF-Kappa B Signalling in Cancer Cells.
abstract: 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- κ B 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- κ B, 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- κ B 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Vincent Kam Wai
authors.initials: VK
authors.lastname: Wong
authors.forename: Molly Miao
authors.initials: MM
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Kelly Yin Ching
authors.initials: KY
authors.lastname: Lam
authors.forename: Po Ling
authors.initials: PL
authors.lastname: Chan
authors.forename: Carmen Ka Man
authors.initials: CK
authors.lastname: Law
authors.forename: Patrick Ying Kit
authors.initials: PY
authors.lastname: Yue
authors.forename: Liang
authors.initials: L
authors.lastname: Liu