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01 February 2020 : Laboratory Research  

Bauerane Induces S-Phase Cell Cycle Arrest, Apoptosis, and Inhibition of Proliferation of A549 Human Lung Cancer Cells Through the Phosphoinositide 3-Kinase (PI3K)/AKT and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway

Qin Chen1BCDEF, Ming Wang2BCDE, Chengji Shen3ABCDEFG*

DOI: 10.12659/MSM.919558

Med Sci Monit 2020; 26:e919558

Abstract

BACKGROUND: Bauerane is a triterpenoid derived from the dandelion root (Taraxacum officinale). This study aimed to investigate the effects of bauerane on cell proliferation of A549 human lung cancer cells and the molecular mechanisms involved.

MATERIAL AND METHODS: A549 human lung adenocarcinoma cells and normal MRC-5 lung fibroblasts were grown in culture and treated with increasing doses of bauerane at 0, 2.5, 5, 10, 20, 40, 80, and 160 µM. The MTT assay was used to measure cell proliferation. Cell apoptosis was assessed by 4’, 6-diamidino-2-phenylindole (DAPI), and acridine orange/ethidium bromide (AO/EB) staining. The cell cycle was evaluated by flow cytometry. Western blot measured the protein expression levels of cytochrome c, Bax, cyclin B1, Bcl-2, PI3K, p-PI3K, Akt, p-Akt, and STAT3 proteins.

RESULTS: Bauerane inhibited the proliferation of A549 lung cancer cells in a dose-dependent manner, with an IC₅₀ of 10 µM, with no cytotoxicity for MRC-5 cells. Bauerane treatment induced apoptosis of A549 cells, which was associated with the upregulation of Bax and down-regulation of Bcl-2. Bauerane induced S-phase arrest of A549 cells, which was dose-dependent and associated with reduced expression of cyclin B1. The findings from Western blot showed that bauerane inhibited the phosphorylation of PI3K/AKT and STAT3 signaling pathways.

CONCLUSIONS: Bauerane inhibited the proliferation of A549 lung cancer cells in vitro and induced cell apoptosis and cell cycle arrest in a dose-dependent manner.

Keywords: Cell Cycle Checkpoints, A549 cells, Cell Nucleus Shape, Cyclin B1, phosphatidylinositol 3-kinase, Proto-Oncogene Proteins c-akt, S Phase, STAT3 Transcription Factor

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750