Anti-metastatic effect of semi-purified Nuphar lutea leaf extracts

Janet Ozer, Daniel Fishman, Brit Eilam, Avi Golan-Goldhirsh, Jacob Gopas

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Nuphar lutea L. SM., leaf and rhizome extracts (NUP), contain nupharidines as active components. Nupharidines belong to the sesquiterpene lactones class of a naturally occurring plant terpenoids. This family of compounds has gained considerable interest for treating infection, inflammation and cancer. NF-κB is a central, downstream regulator of inflammation, cell proliferation and apoptosis. In our previous work we demonstrated strong inhibition of NF-κB activity and induction of apoptosis by NUP. In addition, NUP exhibited anti-inflammatory properties and partial protection from LPS-induced septic shock by modulating ERK pathway and cytokine secretion in macrophages. In the present study, we examined the effect of NUP in a B16 melanoma experimental murine lung metastasis model and its ability to affect the ERK and NF-κB pathways in variety of cell lines. We showed that NUP and cisplatin combined treatment was synergistic and reduced the lung metastatic load. In addition NUP treatment inhibited TNFα-induced IκBα degradation and NF-κB nuclear translocation. We also observed that NUP induced ERK activation. Furthermore, ERK inhibition prevented NF-κB inactivation by NUP. Overall, our work implies that co-administration of NF-κB inhibitors such as NUP, with standard anti-cancer drugs, may act as "sensitizers" for more effective chemotherapy.

Original languageEnglish
Pages (from-to)1433-1440
Number of pages8
JournalJournal of Cancer
Issue number8
StatePublished - 1 Jan 2017


  • ERK
  • Melanoma
  • NF-κB
  • Nuphar lutea plant extract
  • Nupharidines

ASJC Scopus subject areas

  • Oncology


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