State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China.
Eur J Pharmacol. 2018 Jul 5;830:17-25. doi: 10.1016/j.ejphar.2018.04.020. Epub 2018 Apr 19.
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 ICs 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.
非小细胞肺癌（NSCLC）是最常见的癌症类型之一，也是全球癌症相关死亡的主要原因之一，因此发现新的有效药物对于提高生存率仍然至关重要。那拉内酯 E（NLE）是从罗汉松种子中分离出来的一种天然产物，曾被用作食用油和工业油的原料。本研究旨在探讨 NLE 对 NSCLC A549 和 NCI-H1975 细胞的抗癌潜力。MTT 检测显示，NLE 对 A549 和 NCI-H1975 细胞的增殖具有抑制作用，IC50 值分别为 5.18±0.49 和 3.57±0.29µM。NLE 处理抑制了这两种癌细胞系的集落形成。细胞周期分析表明，NLE 处理可有效诱导 A549 和 NCI-H1975 细胞的 G2 期细胞周期停滞。NLE 呈浓度和时间依赖性地下调 cdc2（Tyr15）和 cdc25C（Ser216）的磷酸化以及蛋白激酶 Wee1 的表达水平。此外，NLE 处理降低了 Cyclin B1 的蛋白水平及其核定位，这可能降低了 Cyclin B1/cdc2 复合物的活性并诱导 G2 期停滞。长期 NLE 处理还诱导了 caspase 依赖性细胞凋亡，这表现为 Annexin V 阳性细胞的增加和 PARP 的裂解。总之，NLE 抑制 NSCLC 细胞的增殖，诱导 G2 期停滞，并引发 caspase 依赖性细胞凋亡，提示其可能成为癌症治疗的潜在先导化合物。
