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KMID : 0613820190290030295
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Journal of Life Science
2019 Volume.29 No. 3 p.295 ~ p.302
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Anti-proliferation, Cell Cycle Arrest, and Apoptosis Induced by Natural Liquiritigenin from Licorice Root in Oral Squamous Cell Carcinoma Cells
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Kwak Ah-Won
Yoon Goo
Chae Jung-Il
Shim Jung-Hyun
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Abstract
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Liquiritigenin (LG) is a chiral flavonoid isolated from the roots of licorice. It exhibits multiple biological activities including anti-oxidant, anti-cancer, and anti-inflammatory effects. In particular though, the anti-cancer activity of LG in oral squamous cell carcinoma has yet to be elucidated, and LG-induced apoptosis in oral squamous cell carcinoma remains poorly understood. In the present study, we tested the role of LG in inducing apoptosis in oral squamous cell carcinoma cells. LG treatment of HN22 cells resulted in a dose-dependent inhibition of cell viability as detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. The induction of apoptosis in terms of Annexin V/7-Aminoactinomycin D staining, sub-G1 population, and multi-caspase activity were assessed with a MuseTM Cell Analyzer. Flow cytometric analysis revealed that LG treatment resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and CDC2 expression in a concentration- dependent manner. It also resulted in significant upregulation of p27. In addition, LG was seen to trigger the generation of reactive oxygen species and induce CCAAT/enhancer-binding protein homologous protein and 78-kDa glucose-regulated protein in concentration-dependent upregulation. The LG treatment of HN22 cells led to a loss of mitochondrial membrane potential (△Ψm); it also reduced the levels of anti-apoptotic protein and increased the expression of apoptotic protease activating factor-1, cleaved poly (ADP-ribose)polymerase and Bax. Overall, our results indicate that the pro-apoptotic effects of LG in HN22 cells depend on the activation of both intrinsic and extrinsic signaling pathways. Thus, our results suggest that LG constitutes a natural compound with a potential role as an anti-tumor agent in oral squamous cell carcinoma.
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KEYWORD
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Apoptosis, Liquiritigenin, oral squamous cell carcinoma, reactive oxygen species
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