1. PDB-1 from Potentilla discolor Bunge induces apoptosis and autophagy by downregulating the PI3K/Akt/mTOR signaling pathway in A549 cells.
- Author
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Zhang RR, Meng NN, Liu C, Li KL, Wang MX, Lv ZB, Chen SY, Guo X, Wang XK, Wang Q, and Sun JY
- Subjects
- A549 Cells, Antineoplastic Agents, Phytogenic isolation & purification, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins metabolism, Autophagy-Related Proteins genetics, Autophagy-Related Proteins metabolism, Cell Proliferation drug effects, G2 Phase Cell Cycle Checkpoints drug effects, Gene Expression Regulation, Neoplastic, HeLa Cells, Hep G2 Cells, Humans, Lung Neoplasms genetics, Lung Neoplasms metabolism, Lung Neoplasms pathology, MCF-7 Cells, Plant Extracts isolation & purification, Signal Transduction, Triterpenes isolation & purification, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis drug effects, Autophagy drug effects, Lung Neoplasms drug therapy, Phosphatidylinositol 3-Kinase metabolism, Plant Extracts pharmacology, Potentilla chemistry, Proto-Oncogene Proteins c-akt metabolism, TOR Serine-Threonine Kinases metabolism, Triterpenes pharmacology
- Abstract
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., (Copyright © 2020. Published by Elsevier Masson SAS.)- Published
- 2020
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