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PDB-1 from Potentilla discolor Bunge suppresses lung cancer cell migration and invasion via FAK/Src and MAPK signaling pathways

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Abstract

Lung cancer is the primary reason of cancer death worldwide, with an annual incidence of ~1.3 million cases. Therefore, finding better and more effective methods to treat lung cancer has become very pressing. PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge and is a type of compound that is rarely found in natural sources. This research investigated the effects of a novel triterpenoid compound PDB-1 on the expression of proteins regulating cancer proliferation, migration, and invasion in A549 and H460 cells. The results showed that PDB-1 inhibited the proliferation of A549 and H460 cells and that this inhibition was accompanied by decreased PCNA. Wound, transwell migration, and invasion assays showed that cell migration and invasion of lung cancer cells were significantly inhibited by PDB-1 in a dose-dependent manner. The results of western blot showed that PDB-1 decreased the level of p-FAK, which lead to the downregulation of MMP-2 and MMP-9 and decreased the potential for metastasis. Furthermore, after cells were treated with PDB-1, the expression levels of p-p38, p-ERK, and p-JNK were also dramatically decreased. Simultaneously, this study firstly showed that the PDB-1 can suppress the activation of the ERK/MAPK signaling pathway by inhibiting FAK expression, accordingly inhibiting the proliferation, migration, and invasion of lung cancer cells. Our study offered a molecular foundation for the potential application of PDB-1 on the therapy of lung cancer and the development of new antitumor drugs.

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Acknowledgements

This study was supported by the Major Scientific and Technological Innovation Project of Shandong, China (No. 2019JZZY020612); the Provincial Key Research and Development Program of Shandong, China, (No. 2019JZZY020612, 2018GNC110008, 2019LYXZ011, and 2019LYXZ025); the Provincial Natural Science Foundation of Shandong, China (ZR2019MC072); and the Taishan Scholars’s Program of Shandong for Jin-yue Sun.

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  1. These authors contributed equally: Na-na Meng, Rui-rui Zhang

Authors and Affiliations

  1. Shandong Province Key Laboratory of Plant Stress, College of Life Sciences, Shandong Normal University, No.88, East Wenhua Road, Jinan, 250014, Shandong, PR China

    Na-na Meng, Ping-ping Wang & Jin-yue Sun

  2. Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan, PR China

    Na-na Meng, Rui-rui Zhang, Chao Liu, Qing Wang, Xin-kun Wang, Xu Guo & Jin-yue Sun

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  1. Na-na Meng
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Correspondence to Chao Liu, Ping-ping Wang or Jin-yue Sun.

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Meng, Nn., Zhang, Rr., Liu, C. et al. PDB-1 from Potentilla discolor Bunge suppresses lung cancer cell migration and invasion via FAK/Src and MAPK signaling pathways. Med Chem Res 29, 887–896 (2020). https://doi.org/10.1007/s00044-020-02527-2

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