PDB-1 from Potentilla discolor Bunge induces apoptosis and autophagy by downregulating the PI3K/Akt/mTOR signaling pathway in A549 cells

文献类型： 外文期刊

第一作者： Zhang, Rui-rui

作者： Zhang, Rui-rui;Meng, Na-na;Liu, Chao;Li, Kui-lin;Wang, Mu-xuan;Guo, Xu;Wang, Xin-kun;Wang, Qing;Sun, Jin-yue;Meng, Na-na;Lv, Zhi-bo;Chen, Shu-ya

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关键词： PDB-1; Proliferation; Apoptosis; Autophagy; PI3K/Akt/mTOR; Molecular mechanism

期刊名称：BIOMEDICINE & PHARMACOTHERAPY （ 影响因子：6.529； 五年影响因子：5.979 ）

ISSN： 0753-3322

年卷期： 2020 年 129 卷

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收录情况： SCI

摘要： PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge. In our previous research, PDB-1 was suggested to have an obvious selectivity for tumor cells. This study focused on clarifying PDB-1's anticancer mechanism in the inhibition of proliferation and in the induction of apoptosis and autophagy in A549 cells. In general, A549 cells were treated with PDB-1 for different times, and cell survival was assessed by a CCK8 assay. The assessment of intracellular reactive oxygen species, a mitochondrial membrane potential assay, a cell cycle assay, an annexin V-FITC/PI assay, and MDC staining were performed in A549 cells treated with PDB-1. Moreover, the mRNA and protein expression of cell cycle-, apoptosis- and autophagy-related factors were detected by RT-qPCR and western blotting. The results showed that PDB-1 inhibited A549 cell proliferation and colony formation in a dose- and time-dependent manner. The decrease in the viability of A549 cells was due to a G2/M cell cycle arrest. Moreover, PDB-1 induced cell apoptosis, accompanied by an increase in the Bax/Bcl-2 ratio and an increase in the expression levels of cleaved caspase-3/caspase-9. We also found that PDB-1 induced autophagy by increasing the conversion of LC3-I to LC3-II and elevating Beclin-1. In addition, further studies indicated that pretreatment with a specific PI3K inhibitor (LY294002) enhanced the effects of PDB-1 on the expression of proteins associated with apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway was related to PDB-1-induced apoptosis and autophagy. These results indicated that PDB-1 may be considered a potential candidate for the future treatment of lung adenocarcinoma. These findings should benefit the development of the C-14-COOH type of pentacyclic triterpenoids.

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