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      Cucurbitacin B suppresses metastasis mediated by reactive oxygen species (ROS) via focal adhesion kinase (FAK) in breast cancer MDA-MB-231 cells

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          Abstract

          Metastasis is responsible for the majority of cancer-related deaths and prevention of metastasis remains a big challenge for cancer therapy. Cucurbitacin B (Cuc B) is a natural triterpenoid with potent anticancer activities while its effect on metastasis remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion assays. Furthermore, the adhesion of cancer cells to endothelial cells was determined. The protein expression was determined by Western blotting. Cuc B (< 100 nmol·L −1) showed no obvious cytotoxicity to MDA-MB-231 cells, but significantly inhibited migration, invasion, and adhesion to Matrigel, fibronectin, type I collagen, and endothelial cells. Cuc B dramatically inhibited the phosphorylation of focal adhesion kinase (FAK) and paxillin in dose- and time-dependent manners. Furthermore, Cuc B induced intracellular reactive oxygen species (ROS) generation, which could be reduced by N-acetyl-l-cysteine (NAC). In addition, NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on paxillin expression. In summary, Cuc B suppressed ROS-dependent metastasis through FAK pathway in breast cancer MDA-MB-231 cells, demonstrating novel mechanisms for the anticancer effects of Cuc B.

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          Author and article information

          Journal
          CJNM
          Chinese Journal of Natural Medicines
          Elsevier
          1875-5364
          20 January 2018
          : 16
          : 1
          : 10-19
          Affiliations
          1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao 999078, China
          Author notes
          *Corresponding author: WANG Yi-Tao, Tel: 853-88224679; 853-88224691, E-mails: ytwang@ 123456umac.mo , CHEN Xiu-Ping, xpchen@ 123456umac.mo

          These authors have no conflict of interest to declare.

          Article
          S1875-5364(18)30025-6
          10.1016/S1875-5364(18)30025-6
          29425586
          Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funding
          Funded by: Science and Technology Development Fund, Macao S.A.R (FDCT)
          Award ID: 039/2014/ A1
          Funded by: Research Fund of University of Macau
          Award ID: CPG2014-00012-ICMS
          Award ID: MYRG2016-00043-ICMS-QRCM
          Award ID: MYRG2015- 00091-ICMS-QRCM
          This work was supported by the Science and Technology Development Fund, Macao S.A.R (FDCT) (No. 039/2014/ A1), and the Research Fund of University of Macau (Nos. CPG2014-00012-ICMS, MYRG2016-00043-ICMS-QRCM, and MYRG2015- 00091-ICMS-QRCM).

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