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Novel FTS-diamine/cinnamic acid hybrids inhibit tumor cell proliferation and migration and promote apoptosis via blocking Ras-related signaling in vitro

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Abstract

Novel FTS-diamine/cinnamic acid hybrids 7a–f were prepared, and their in vitro biological activities were evaluated. It was found that 7c showed the strongest anti-proliferation activities against cancer cells in vitro and significant growth inhibition of tumor in vivo, and more potential for inhibitory selectivity to tumor cells than intermediate 6 and FTS. Furthermore, the anti-proliferative effect of 7c in Lovo cell lines followed a similar pattern, which included a dose-dependent induction of cell apoptosis via the up-regulation of Bax as well as activated caspase-3 and down-regulation of Bcl-2, and the inhibition of cancer cells migration and invasion in a concentration-dependent way. More importantly, 7c could significantly block Ras-related signaling pathways, which may contribute to its pro-apoptotic induction of the cancer cell lines and its inhibition of carcinoma cell proliferation, migration, and invasion. Therefore, our novel findings may provide a new framework for the discovery of new FTS hybrids for the intervention of human carcinoma cells.

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Acknowledgments

We gratefully acknowledge the financial support by the Natural Science Foundation of China (Grant No. 81302628) and the Project of “Jiangsu Six Peaks of Talent” (2014-SWYY-044), China Postdoctoral Science Foundation (2013M541707), China Pharmaceutical University for the Open Project Program of State Key Laboratory of Natural Medicines (SKLNMKF201415), and also thank a project funded by the Priority Academic Programs Development of Jiangsu Higher Education Institutions (PAPD).

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The authors have no conflict of interest.

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Authors and Affiliations

  1. School of Pharmacy, Nantong University, Nantong, 226001, People’s Republic of China

    Yong Ling, Xinmei Zhao, Xianghua Li, Xuemin Wang, Yang Yang, Zhiqiang Wang & Xinyang Wang

  2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Yong Ling, Zhiqiang Wang & Yihua Zhang

  3. The Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, People’s Republic of China

    Jie Zhang

  4. School of Life Sciences, Xinyang Normal University, Xinyang, 464000, People’s Republic of China

    Xinmei Zhao

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  1. Yong Ling
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  2. Xinmei Zhao
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  3. Xianghua Li
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  4. Xuemin Wang
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  5. Yang Yang
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  8. Jie Zhang
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  9. Yihua Zhang
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Correspondence to Jie Zhang.

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Ling, Y., Zhao, X., Li, X. et al. Novel FTS-diamine/cinnamic acid hybrids inhibit tumor cell proliferation and migration and promote apoptosis via blocking Ras-related signaling in vitro. Cancer Chemother Pharmacol 75, 381–392 (2015). https://doi.org/10.1007/s00280-014-2650-2

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  • DOI: https://doi.org/10.1007/s00280-014-2650-2

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