Jacob Gopas
Soroka University Medical Center, Israel
Title: Nupharidines Enriched Leaf Extract of Nuphar lutea Reduces Experimental Melanoma Metastases
Biography
Biography: Jacob Gopas
Abstract
Nuphar lutea L. SM., leaf and rhizome extracts (NUP), contain nupharidines as active ingredients. 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-кB is a central, downstream regulator of inflammation, cell proliferation and apoptosis. In our previous work we demonstrated strong inhibition of NF-кB 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-кB 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 IкBa degradation and NF-кB nuclear translocation. We also observed that NUP induced ERK activation. Furthermore, ERK inhibition prevented NF-кB inactivation by NUP. Interestingly, NUP treatment induced ERK activation in a human melanoma cell line, expressing BRAF mutation. Overall, our work implies that co-administration of NF-кB inhibitors with standard anticancer drugs or radiotherapy, may act as sensitizers or as inhibitors of multidrug resistance.