J Cancer 2017; 8(8):1433-1440. doi:10.7150/jca.18435

Research Paper

Anti-Metastatic Effect of Semi-Purified Nuphar Lutea Leaf Extracts

Janet Ozer1✉, Daniel Fishman2, Brit Eilam1, Avi Golan-Goldhirsh4*, Jacob Gopas1, 3*

1. The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences Ben-Gurion University of the Negev, Beer Sheva, Israel;
2. Department of Physiology and Cell Biology, Faculty of Health Sciences Ben-Gurion University of the Negev, Beer Sheva, Israel;
3. Dept. of Oncology, Soroka University Medical Center, Beer Sheva, Israel;
4. The Jacob Blaustein Institutes for Desert Research (BIDR), French Associates Institute for Agriculture and Biotechnology of Drylands, Sede Boqer Campus 84990 Israel.
* AGG and JG contributed equally to this work.

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Ozer J, Fishman D, Eilam B, Golan-Goldhirsh A, Gopas J. Anti-Metastatic Effect of Semi-Purified Nuphar Lutea Leaf Extracts. J Cancer 2017; 8(8):1433-1440. doi:10.7150/jca.18435. Available from https://www.jcancer.org/v08p1433.htm

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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.

Keywords: Nuphar lutea plant extract, nupharidines, melanoma, ERK, NF-κB.