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橙花醇通过 TNF-α 通路和活性氧积累诱导人肺癌细胞发生坏死性凋亡。

Citronellol Induces Necroptosis of Human Lung Cancer Cells TNF-α Pathway and Reactive Oxygen Species Accumulation.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Changhwa Christian Hospital, Changhwa, Taiwan, R.O.C.

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.

出版信息

In Vivo. 2019 Jul-Aug;33(4):1193-1201. doi: 10.21873/invivo.11590.

Abstract

BACKGROUND/AIM: Our current study aimed to determine the molecular mechanisms of citronellol-induced cell death and ROS accumulation in non-small cell lung cancer (NCI-H1299 cells) and also compare the anticancer effects of citronellol and EOPC.

MATERIALS AND METHODS

ROS measurement and western blotting were performed to detect whether citronellol can induce necroptosis in vitro. Besides, we performed an in vivo analysis of tumourigenesis inhibition by citronellol treatment in BALB/c (nu/nu) nude mice.

RESULTS

Necroptosis occured by up-regulating TNF-α, RIP1/RIP3 activities, and down-regulating caspase-3/caspase-8 activities after citronellol treatment in NCI-H1299 cells. Citronellol also resulted in a biphasic increase in ROS production at 1 h and at 12 h in NCI-H1299 cells. Xenograft model experiments showed that citronellol could effectively inhibit subcutaneous tumours produced 4 weeks after intraperitoneal injection of NCI-H1299 in BALB/c nude mice.

CONCLUSION

Citronellol induced necroptosis of NCI-H1299 cells via TNF-α pathway and ROS accumulation.

摘要

背景/目的:本研究旨在探讨香芹醇诱导非小细胞肺癌(NCI-H1299 细胞)细胞死亡和 ROS 积累的分子机制,并比较香芹醇和 EOPC 的抗癌作用。

材料与方法

通过 ROS 测量和 Western blot 检测香芹醇是否能在体外诱导细胞发生坏死性凋亡。此外,我们还在 BALB/c(nu/nu)裸鼠中进行了香芹醇治疗抑制肿瘤发生的体内分析。

结果

香芹醇处理后,NCI-H1299 细胞中 TNF-α、RIP1/RIP3 活性上调,caspase-3/caspase-8 活性下调,导致坏死性凋亡。香芹醇还导致 NCI-H1299 细胞在 1 h 和 12 h 时出现双峰式 ROS 产生增加。异种移植模型实验表明,香芹醇可有效抑制腹腔注射 NCI-H1299 后 4 周 BALB/c 裸鼠皮下肿瘤的生长。

结论

香芹醇通过 TNF-α 途径和 ROS 积累诱导 NCI-H1299 细胞发生坏死性凋亡。

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