Program

PO3-7-17

Downregulation of Cyclin B1 Mediated Nagilactone E-Induced G2 Phase Cell Cycle Arrest in Non-Small Cell Lung Cancer Cells

[Speaker] Jin-Jian Lu:1
[Co-author] Le-Le Zhang:1, Zhe-Ling Feng:1, Min-Xia Su:1, Xiuping Chen:1, Ao Li:2, Li-Gen Lin:1
1:University of Macau, China, 2:Chongqing University of Technology, China

Non-small cell lung cancer (NSCLC) is one of most common forms and leading causes of cancer-related mortality worldwide. Discovery of new effective drugs still remains imperative for the improvement of the survival rate. This study aims to investigate the anticancer potential of a natural product Nagilactone E (NLE) against epidermal growth factor receptor (EGFR) wild-type A549 and EGFR T790M mutant NCI-H1975 cells. NLE inhibited proliferation of A549 and NCI-H1975 cells with IC50s of 5.18 μM and 3.57 μM, respectively. Treatment with NLE obviously inhibited clone formation in both cancer cell lines. Analysis of the distribution of cell cycle showed that 24 h treatment of NLE effectively induced G2 phase cell cycle arrest in A549 and NCI-H1975 cells. NLE down-regulated the phosphorylation of cdc2 Tyr15 and cdc25C Ser216, and the expression level of the protein kinase Wee1 in dose- and time-dependent manner. Meanwhile, NLE treatment decreased the protein level of cyclin B1 as well as its nuclear localization, which might result in the decrease of activity of cyclin B1/cdc2 complex and induced G2 phase arrest. Besides, long time treatment of NLE also induced cell apoptosis, as evidenced by increased Annexin V positive cells and the cleavage of PARP. NLE inhibited proliferation, induced G2 phase arrest and apoptosis in EGFR wild-type A549 and EGFR T790M mutant NCI-H1975 cells, it possessed anti-cancer potential as a single agent against non-small cell lung cancer.
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