Bergapten induces G1 arrest of non‑small cell lung cancer cells, associated with the p53‑mediated cascade

Chiang,Shyh‑Ren; Lin,Chun‑Shiang; Lin,Hui‑Han; Shieh,Pei‑Chen; Kao,Shao‑Hsuan

doi:10.3892/mmr.2019.9810

Bergapten induces G1 arrest of non‑small cell lung cancer cells, associated with the p53‑mediated cascade

Authors:
- Shyh‑Ren Chiang
- Chun‑Shiang Lin
- Hui‑Han Lin
- Pei‑Chen Shieh
- Shao‑Hsuan Kao
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Affiliations: Department of Internal Medicine, Chi Mei Medical Center, Tainan 710, Taiwan, R.O.C., Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C., Surgical Department, Cardiovascular Division, China Medical University Hospital, Taichung 402, Taiwan, R.O.C.
Published online on: January 2, 2019 https://doi.org/10.3892/mmr.2019.9810
Pages: 1972-1978

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Abstract

The principal subtype of lung cancer, non‑small cell lung cancer (NSCLC) is a life‑threatening malignancy that causes high mortality rates. Bergapten (5‑methoxypsoralen) has been identified to possess anticancer activity against a number of carcinomas. In the present study, the effects of bergapten on NSCLC cells were investigated. The cell viability was determined by MTT assay. Cell cycle distribution was analyzed using flow cytometry. Protein expression and kinase cascade were demonstrated using western blot analysis. The results demonstrated that treatment with bergapten (50 µM for 48 h) inhibited the viability of A549 and NCI‑H460 NSCLC cells to 79.1±2.8% and 74.5±3.1%, respectively, compared with the controls. It was identified that bergapten induced G1 phase accumulation in A549 and NCI‑H460 cells between ~58 and 75% (P<0.01). In addition, bergapten significantly increased the sub‑G1 phase ratio to ~9% (P<0.05) in the two cell types. Further investigation demonstrated that bergapten upregulated the expression of cellular tumor antigen p53 (p53) and its downstream proteins cyclin‑dependent kinase inhibitor 1 and cyclin‑dependent kinase inhibitor 1B, whereas, it downregulated the expression of cyclin D1 and CDK4. Overall, these results suggested that bergapten may inhibit cell viability and trigger G1 arrest and apoptosis in A549 and NCI‑H460 cells, which may be attributed to the activation of p53‑mediated cascades. Therefore, bergapten may be beneficial for NSCLC treatment.

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