Backgrounds

Arctigenin derived from the seeds of Arctium lappa Linnaeus is known as an anticancer drug candidate by targeting various pathways involved in anticancer therapy.

Methods

Using 2D monolayer and 3D spheroid culture systems in nasal septum carcinoma RPMI-2650 cells, the effects of arctigenin and dexamethasone on cell viability, ROS levels, ATP level, mitochondrial function, apoptosis and necroptosis were examined.

Results

The combination treatment of both compounds induced strong cytotoxicity, accompanied by increases of sub-G₀/G₁ peak, annexin V-PE-positive cells, and ROS levels, loss of mitochondrial membrane potential, and decrease of cellular ATP content. These changes were observed as simultaneous induction of DNA damage, apoptosis, and necroptosis. A series of changes by arctigenin and dexamethasone were efficiently restored by decreasing ROS levels or supplementing ATP. Treatment of 3D spheroids with arctigenin and dexamethasone decreased cell viability in the spheroids, but it was slightly resistant than cells under 2D conditions. In addition, this phenomenon was accompanied by an increase in mediators for both apoptosis and necroptosis.

Conclusion

Results of this study suggest that the apoptosis and necroptosis-inducing effects of arctigenin are associated with ATP depletion due to oxidative mitochondrial dysfunction.

中文翻译：

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阿奇霉素原对2D和3D鼻中隔癌RPMI-2650细胞凋亡和坏死的诱导作用

背景资料

牛蒡苷元衍生自种子蒡Linnaeus的是通过靶向参与抗癌治疗各种途径已知作为抗癌药物候选。

方法

使用2D单层和3D球状培养系统处理鼻中隔RPMI-2650细胞，检查了Arctigenin和地塞米松对细胞活力，ROS水平，ATP水平，线粒体功能，细胞凋亡和坏死性坏死的影响。

结果

两种化合物的联合处理均具有很强的细胞毒性，并伴有sub-G ₀ / G ₁峰，膜联蛋白V-PE阳性细胞和ROS含量增加，线粒体膜电位丧失和细胞ATP含量降低。观察到这些变化是同时诱导DNA损伤，细胞凋亡和坏死病。通过降低ROS水平或补充ATP，有效地恢复了Arctigenin和地塞米松引起的一系列变化。用Arctigenin和地塞米松处理3D球体会降低球体中的细胞活力，但比2D条件下的细胞稍具抵抗力。另外，这种现象伴随着凋亡和坏死病介体的增加。

结论

这项研究的结果表明，Arctigenin的凋亡和坏死病诱导作用与氧化性线粒体功能障碍引起的ATP消耗有关。