Phiboonchaiyanan Preeyaporn Plaimee, Petpiroon Nalinrat, Sritularak Boonchoo, Chanvorachote Pithi
Department of Pharmacology, Faculty of Pharmacy, Rangsit University, Pathumthani, Thailand.
Cell-based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Anticancer Res. 2018 Nov;38(11):6281-6290. doi: 10.21873/anticanres.12984.
BACKGROUND/AIM: Lung cancer is by far the most common cause of cancer mortality, accounting for nearly 20% of all global cancer deaths. Therefore, potent and effective compounds for treatment of this cancer type are essential. Phoyunnanin E, isolated from Dendrobium venustum (Orchidaceae), has promising pharmacological activities; however, it is unknown if phoyunnanin E affects apoptosis of lung cancer cells.
The apoptosis-inducing activity of phoyunnanin E on H460 lung cancer cells was investigated by Hoechst 33342, and annexin V-fluorescein isothiocyanate/propidium iodide staining. The underlying mechanism was determined via monitoring apoptosis-regulatory proteins by western blot analysis. The apoptotic effect of the compound was confirmed in H23 lung cancer cells.
Phoyunnanin E significantly induced apoptotic cell death of H460 lung cancer cells, as indicated by condensed and fragmented nuclei with the activation of caspase-3 and -9 and poly (ADP-ribose) polymerase cleavage. Phoyunnanin E mediated apoptosis via a p53-dependent pathway by increasing the accumulation of cellular p53 protein. As a consequence, anti-apoptotic proteins including induced myeloid leukemia cell differentiation protein (MCL1) and B-cell lymphoma 2 (BCL2) were found to be significantly depleted, while pro-apoptotic BCL-2-associated X protein (BAX) protein was up-regulated. Furthermore, it was found that expression of an inhibitor of apoptosis, survivin, markedly reduced in response to phoyunnanin E treatment. The apoptosis-inducting effect was also found in phoyunnanin E-treated H23 lung cancer cells.
These results indicate the promising effect of phoyunnanin E in induction of apoptosis, that may be useful for the development of novel anticancer agents.
背景/目的：肺癌是目前癌症死亡的最常见原因，占全球所有癌症死亡人数的近20%。因此，用于治疗这种癌症类型的强效且有效的化合物至关重要。从秀丽兜兰（兰科）中分离出的滇南素E具有良好的药理活性；然而，滇南素E是否影响肺癌细胞的凋亡尚不清楚。
通过Hoechst 33342以及膜联蛋白V-异硫氰酸荧光素/碘化丙啶染色研究滇南素E对H460肺癌细胞的凋亡诱导活性。通过蛋白质印迹分析监测凋亡调节蛋白来确定其潜在机制。在H23肺癌细胞中证实了该化合物的凋亡作用。
滇南素E显著诱导H460肺癌细胞发生凋亡性细胞死亡，表现为细胞核浓缩和碎片化，同时伴有半胱天冬酶-3和-9的激活以及聚（ADP-核糖）聚合酶的切割。滇南素E通过增加细胞p53蛋白的积累，经由p53依赖途径介导凋亡。结果发现，包括诱导髓系白血病细胞分化蛋白（MCL1）和B细胞淋巴瘤2（BCL2）在内的抗凋亡蛋白显著减少，而促凋亡的BCL-2相关X蛋白（BAX）蛋白上调。此外，还发现凋亡抑制蛋白生存素的表达在滇南素E处理后明显降低。在滇南素E处理的H23肺癌细胞中也发现了凋亡诱导作用。
这些结果表明滇南素E在诱导凋亡方面具有良好的效果，这可能有助于新型抗癌药物的开发。
