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.
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.