Downregulation of Cyclin B1 mediates nagilactone E-induced G2 phase cell cycle arrest in non-small cell lung cancer cells. 2018

Le-Le Zhang, and Zhe-Ling Feng, and Min-Xia Su, and Xiao-Ming Jiang, and Xiuping Chen, and Yitao Wang, and Ao Li, and Li-Gen Lin, and Jin-Jian Lu
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.

Non-small cell lung cancer (NSCLC) is one of the most common forms and leading causes of cancer-related mortality worldwide, and discovery of new effective drugs still remains imperative to improve the survival rate. Nagilactone E (NLE) is a natural product isolated from Podocarpus nagi seeds, which has been used as raw materials for edible oil and industrial oil extraction. This study aimed to investigate the anticancer potential of NLE against NSCLC A549 and NCI-H1975 cells. MTT assay revealed that NLE inhibited the proliferation of A549 and NCI-H1975 cells with IC50s of 5.18 ± 0.49 and 3.57 ± 0.29 μM, respectively. NLE treatment inhibited clone formation in both cancer cell lines. Cell cycle analysis indicated that NLE treatment effectively induced G2 phase cell cycle arrest in A549 and NCI-H1975 cells. NLE downregulated the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser216) as well as the expression level of the protein kinase Wee1 in concentration- and time-dependent manners. In addition, NLE treatment decreased the protein level of Cyclin B1 as well as its nuclear localization, which might decrease the activity of the Cyclin B1/cdc2 complex and induce G2 phase arrest. Long-term NLE treatment also induced caspase-dependent cell apoptosis, as evidenced by increase in Annexin V positive cells and the cleavage of PARP. To sum, NLE inhibited proliferation, induced G2 phase arrest, and triggered caspase-dependent apoptosis in NSCLC cells, suggesting it to be a potential leading compound for cancer treatment.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D002289 Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D056744 Cyclin B1 A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
D059565 G2 Phase Cell Cycle Checkpoints CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE. Antephase Checkpoint,G2 Cell Cycle Arrest,G2 Cell Cycle Checkpoints,G2 Cell Cycle Control,G2 Phase Checkpoints,G2 Restriction Point,G2-M Cell Cycle Checkpoint,Antephase Checkpoints,Checkpoint, Antephase,Checkpoint, G2 Phase,Checkpoints, Antephase,Checkpoints, G2 Phase,G2 M Cell Cycle Checkpoint,G2 Phase Checkpoint,G2 Restriction Points,Restriction Point, G2,Restriction Points, G2

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