Ozer Janet, Fishman Daniel, Eilam Brit, Golan-Goldhirsh Avi, Gopas Jacob
The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences Ben-Gurion University of the Negev, Beer Sheva, Israel.
Department of Physiology and Cell Biology, Faculty of Health Sciences Ben-Gurion University of the Negev, Beer Sheva, Israel.
J Cancer. 2017 May 12;8(8):1433-1440. doi: 10.7150/jca.18435. eCollection 2017.
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.
L.SM.（莲叶桐属植物的叶和根茎提取物）含有睡莲碱作为活性成分。睡莲碱属于天然存在的植物萜类化合物中的倍半萜内酯类。这类化合物在治疗感染、炎症和癌症方面引起了广泛关注。核因子κB（NF-κB）是炎症、细胞增殖和凋亡的核心下游调节因子。在我们之前的研究中，我们证明了莲叶桐属植物提取物对NF-κB活性有强烈抑制作用，并能诱导细胞凋亡。此外，莲叶桐属植物提取物具有抗炎特性，通过调节巨噬细胞中的细胞外信号调节激酶（ERK）途径和细胞因子分泌，对脂多糖（LPS）诱导的脓毒症休克有部分保护作用。在本研究中，我们检测了莲叶桐属植物提取物在B16黑色素瘤实验性小鼠肺转移模型中的作用，以及其影响多种细胞系中ERK和NF-κB途径的能力。我们发现莲叶桐属植物提取物和顺铂联合治疗具有协同作用，可降低肺转移负荷。此外，莲叶桐属植物提取物处理可抑制肿瘤坏死因子α（TNFα）诱导的IκBα降解和NF-κB核转位。我们还观察到莲叶桐属植物提取物可诱导ERK激活。此外，ERK抑制可阻止莲叶桐属植物提取物对NF-κB的失活作用。总体而言，我们的研究表明，将莲叶桐属植物提取物等NF-κB抑制剂与标准抗癌药物联合使用，可能作为“增敏剂”以实现更有效的化疗。
