Banjerdpongchai Ratana, Khawon Patompong, Pompimon Wialrt
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Email :
Asian Pac J Cancer Prev. 2016;17(7):3281-7.
Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF7 > HeLa > HepG2 > NIH3T3 cells with IC50 values of 7.33, 14.8, 37.1 and 65.4 μM, respectively, whereas PCN was cytotoxic only to HepG2 cells with IC50 values of ~80 μM. Apoptotic cell death was confirmed by staining the cells with annexin VFITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamintreated MCF7 cells in a dose response manner. Positive PIstained cells with the typical morphology of apoptotic cells were increased dosedependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamintreated MCF7, HepG2 and HeLa cells. GTN treatment in MCF7 increased caspase3, 8 and 9 activities while GTNinduced HeLa cells showed an increase of both caspase3 and 9 activities. But an increased caspase8 activity was demonstrated in GTN and PCNtreated MCF7 and HepG2 cells, respectively. Taken together, GTN and PCNinduced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compoundmodulated caspase activities in both intrinsic and/or extrinsic pathways.
从哥纳香（Goniothalamus griffithii）的叶子和嫩枝中提取的生物活性化合物包括松属素（PCN）和哥纳香素（GTN）。本研究的目的是研究PCN和GTN的细胞毒性活性，以及与正常小鼠成纤维细胞NIH3T3细胞相比，它们对几种人类癌细胞系中细胞死亡分子信号传导的影响。GTN对MCF7＞HeLa＞HepG2＞NIH3T3细胞表现出最强的细胞毒性，IC50值分别为7.33、14.8、37.1和65.4 μM，而PCN仅对HepG2细胞具有细胞毒性，IC50值约为80 μM。通过使用流式细胞术用膜联蛋白V FITC和碘化丙啶（PI）对细胞进行染色来确认凋亡细胞死亡。在经哥纳香素处理的MCF7细胞中，磷脂酰丝氨酸的外化以剂量反应方式显示出凋亡。具有典型凋亡细胞形态的PI阳性染色细胞呈剂量依赖性增加。此外，在经哥纳香素处理的MCF7、HepG2和HeLa细胞中发现线粒体跨膜电位降低。GTN处理MCF7增加了caspase-3、8和9的活性，而GTN诱导的HeLa细胞显示caspase-3和9的活性均增加。但在经GTN和PCN处理的MCF7和HepG2细胞中分别证明了caspase-8活性增加。综上所述，GTN和PCN诱导的人类癌细胞凋亡是通过不同的分子机制或信号通路，这可能是由于不同类型癌细胞中的不同机制，这在内在和/或外在途径中化合物调节的caspase活性中得到了证明。
