Sesquiterpene lactone Bigelovin induces apoptosis of colon cancer cells through inducing IKK-β degradation and suppressing nuclear factor kappa B activation

Yuan Feng, Jun Xia, Xin Xu, Tong Zhao, Zhengzhi Tan, Qun Wang, Jun Wang, Jia Meng, Christopher Sanderson, Zhiliang Lu, Yili Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Bigelovin, a sesquiterpene lactone extracted from plant Inula helianthus aquatica, exhibited multiple interesting biological activities, including anti-inflammation, antiangiogenesis and cytotoxic action against cancer cells. In the present study, we found that Bigelovin reduced the viability of human colon cancer cells and induced their apoptosis in a time- and dose-dependent manner, with an IC50-5 μM. RNAseq and luciferase reporter analyses revealed that the nuclear factor kappa B (NF-κB) signaling was one of the most significantly inhibited pathways after Bigelovin treatment. Further systemic examination showed that exposure to Bigelovin resulted in ubiquitination and degradation of inhibitor of kappa-B kinase-beta (IKK-β) and decrease of IκB-α and p65 phosphorylation, which led to the downregulation of NF-κB-regulated genes expression. Moreover, enforced expression of exogenous IKK-β attenuated Bigelovin-induced NF-κB suppression and cell viability reduction. These results indicated that Bigelovin exerts a cytotoxic action against colon cancer cells through the induction of IKK-β degradation and consequently the inhibition of NF-κB signaling. Given the abnormal activation of NF-κB signaling in colorectal cancer (CRC) cells and the critical role of chronic inflammation in CRC development, it is conceivable that at least some colorectal cancer cells are addictive to NF-κB activation and targeting the pathway is an effective anti-CRC strategy.

Original languageEnglish
Pages (from-to)664-673
Number of pages10
JournalAnti-Cancer Drugs
Issue number6
Publication statusPublished - 1 Jun 2021


  • Apoptosis
  • Bigelovin
  • Colorectal cancer
  • Ikk-β
  • Nuclear factor kappa b signaling

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