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山奈酚通过 ROS 和 ERK/MAPK 通路诱导口腔鳞状细胞癌细胞发生PARP 细胞死亡。

Isorhamnetin induces the paraptotic cell death through ROS and the ERK/MAPK pathway in OSCC cells.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Sichuan University, Chengdu, China.

出版信息

Oral Dis. 2021 Mar;27(2):240-250. doi: 10.1111/odi.13548. Epub 2020 Jul 30.

DOI:10.1111/odi.13548
PMID:32654232
Abstract

OBJECTIVE

There were rarely investigations on the effects and molecular mechanisms of oral squamous cell carcinoma (OSCC) cells when treated with isorhamnetin. This article assesses the anti-cancer effect of isorhamnetin.

METHODS AND MATERIALS

Oral squamous cell carcinoma cells were treated with or without isorhamnetin. Cell proliferation, cell cycle arrest, cell migration, cell death, and the related signaling pathways were evaluated.

RESULTS

The results revealed that cell proliferation was inhibited in a dose- and time-dependent manner, which was confirmed by diminished cell viability and revealed by decreased in the number of cell colonies. In addition, the cell cycle arrested in the G2/M phase, and the protein levels of cyclin B1 and CDC2 were suppressed. Moreover, the cell migration was inhibited, and the protein levels of related proteins were modulated. Furthermore, it could be observed that abundant cytoplasmic vacuoles existed which that were derived from mitochondria and the endoplasmic reticulum. It was confirmed that cell death did not result from apoptosis and may have which may be apt to paraptosis. Isorhamnetin was observed to upregulate phosphorylated ERK cascades and increase intracellular reactive oxygen species levels.

CONCLUSIONS

Our study suggested that the anti-cancer effect of isorhamnetin might trigger paraptosis, which may indicate a new therapeutic approach to OSCC.

摘要

目的

关于山奈酚对口腔鳞状细胞癌(OSCC)细胞的作用及分子机制的研究甚少。本文评估了山奈酚的抗癌作用。

方法与材料

用或不用山奈酚处理口腔鳞状细胞癌细胞。评估细胞增殖、细胞周期阻滞、细胞迁移、细胞死亡以及相关信号通路。

结果

结果表明,细胞增殖呈剂量和时间依赖性抑制,细胞活力降低证实了这一点,细胞集落数量减少也证实了这一点。此外,细胞周期被阻滞在 G2/M 期,细胞周期蛋白 B1 和 CDC2 的蛋白水平受到抑制。此外,细胞迁移受到抑制,相关蛋白的蛋白水平发生了调节。此外,还观察到大量源自线粒体和内质网的细胞质空泡。细胞死亡不是由凋亡引起的,可能倾向于发生Paraptosis。山奈酚被观察到上调磷酸化 ERK 级联并增加细胞内活性氧水平。

结论

我们的研究表明,山奈酚的抗癌作用可能引发 Paraptosis,这可能为 OSCC 提供一种新的治疗方法。

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