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.

Abstract

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.

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How to cite this article:
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 http://www.jcancer.org/v08p1433.htm