Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1
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Xin Li1, Shengjun Fan1, Xueyang Pan1,2, Yilixiati Xiaokaiti1, Jianhui Duan1, Yundi Shi1, Yan Pan1, Lu Tie1, Xin Wang2, Yuhua Li1, Xuejun Li1
1State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China
2Current address: University of Minnesota, Twin cities, MN 55455, USA
Xuejun Li, email: [email protected]
Keywords: nordihydroguaiaretic acid, neuropilin 1, cancer cell migration and metastasis, proteomics, prostate cancer
Received: July 18, 2016 Accepted: November 07, 2016 Published: November 15, 2016
Tumor metastasis is a major cause leading to the deaths of cancer patients. Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated to show therapeutic values in multiple diseases. In this study, we report that NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA suppresses NRP1 function by downregulating its expression, which leads to attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells. Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also impairs angiogenesis function of endothelial cells and fibronectin assembly by fibroblasts, both of which are critical to promote metastasis. Based on these comprehensive effects, NDGA effectively suppresses tumor metastasis in nude mice model. Our findings reveal a novel mechanism underlying the anti-metastasis function of NDGA and indicate the potential value of NDGA in NRP1 targeting therapy for selected subtypes of cancer.
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