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

Abstract

Departmental sources 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/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 IC 50 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.

Twist-1 Stimulates the Malignant Behaviors of Hydatidiform Mole via the PI3K/AKT Pathway

“…The PI3K/AKT pathway plays critical roles in cell biological processes, including angiogenesis, proliferation, and apoptosis progression, by influencing the activation states of multiple downstream effectors [28][29][30]. A previous study implied that Twist-1 plays a role in drug resis- tance in chronic myelogenous leukemia by acting on the PI3K/AKT pathway [31].…”

Erdafitinib Inhibits Tumorigenesis of Human Lung Adenocarcinoma A549 by Inducing S-Phase Cell-Cycle Arrest as a CDK2 Inhibitor

“…As a complex sequence of events through which a cell duplicates its contents and divides, abnormal activity of the cell cycle represents a driving force of tumorigenesis [ 18 , 19 , 20 ]. Recently, cell-cycle regulation has become an effective anti-tumor strategy [ 21 , 22 , 23 , 24 ]. Cyclin-dependent kinases (CDKs), the key regulatory enzymes, are involved in cell-cycle checkpoints regulation [ 25 , 26 ].…”

Bioactive Usual and Unusual Triterpenoids Derived from Natural Sources Used in Traditional Medicine

“…The bauerane triterpenoids are less explored in plants. A compound 3 β ‐acetoxybauer‐7‐en‐6‐one ( 131 ) was identified from the methanol extract (at 60 °C for ten days) of the roots of T. officinale , [116] which showed a dose‐dependent inhibition against A549 lung cancer cell proliferation, with an (IC 50 of 10 μM) and no cytotoxicity against MRC‐5 cells [117] …”

“…Several species of the genus Cucurbita are cultivated worldwide as food crops, including guards, bitter guards, melons, squashes, and pumpkins used in traditional medicine to treat various illnesses. 7-oxomultiflor-8-ene-3-29diol 3-acetate-29-benzoate (117) was extracted from the seed of C. maxima L. and showed a potent cytotoxic effect against HL-60 (IC 50 = 7.0 μM) and P388 (IC 50 = 9.5 μM) cells. [98] C. argyrosperma, a Mesoamerican native plant, is known in Mexico as calabaza.…”