Saikosaponin-d enhances the anticancer potency of TNF- α via overcoming its undesirable response of activating NF-kappa B signalling in cancer cells

Vincent Kam Wai Wong, Molly Miao Zhang, Hua Zhou, Kelly Yin Ching Lam, Po Ling Chan, Carmen Ka Man Law, Patrick Y K YUE, Liang LIU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

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-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-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-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.

Original languageEnglish
Article number745295
JournalEvidence-based Complementary and Alternative Medicine
Volume2013
DOIs
Publication statusPublished - 2013

Scopus Subject Areas

  • Complementary and alternative medicine

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