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芝麻素诱导宫颈癌细胞内质网应激介导的细胞凋亡并激活自噬。

Sesamin induces ER stress-mediated apoptosis and activates autophagy in cervical cancer cells.

机构信息

Center of Morphological Experiment, Medical College of Yanbian University, Jilin, China.

Department of Pathology, Affiliated Hospital of Yanbian University, Jilin, China.

出版信息

Life Sci. 2018 May 1;200:87-93. doi: 10.1016/j.lfs.2018.03.003. Epub 2018 Mar 2.

DOI:10.1016/j.lfs.2018.03.003
PMID:29505783
Abstract

AIMS

Sesamin, a major lignan of sesame oil, has demonstrated anticancer properties. However, its anticancer effects on cervical cancer have not been studied. Here, we investigated the effects of sesamin on cervical cancer (HeLa) cell line and explored the underlying mechanisms.

MAIN METHODS

HeLa cells were cultured with sesamin. CCK-8 and scratch wound test were applied to detect the proliferation and migration ability, while flow cytometry and TUNEL staining were applied to detect apoptosis. The expression of Bax and Bcl-2 was assessed by Western blotting. Further observe the ultrastructure using transmission electron microscopy (TEM) and detect the expression of caspase-12, GRP78, GADD153, IRE1α, p-IRE1α, JNK, p-JNK, LC3I/II and beclin-1. In addition, HeLa cells were treated with 3-MA (an autophagy inhibitor) and/or sesamin. Then detect the expression of LC3I/II and cell viability.

KEY FINDINGS

CCK-8 and scratch wound test revealed that sesamin inhibits HeLa cells proliferation and migration, while flow cytometry and TUNEL staining indicated that sesamin induces apoptosis in these cells. In sesamin group, the expression of Bax, caspase-12, GRP78, GADD153, p-IRE1α, p-JNK, LC3I/II and beclin-1 was up-regulated while Bcl-2 was down-regulated compared to control group. Further research revealed that sesamin also induces Hela cells autophagy and inhibition of autophagy increases cell viability of sesamin-treated HeLa cells.

SIGNIFICANCE

Sesamin inhibits proliferation/migration of HeLa cells and induces ER stress-mediated apoptosis through IRE1α/JNK pathway, and that it activates autophagy and autophagic death in these cells, further validate the anticancer effect of sesamin.

摘要

目的

芝麻素是芝麻油中的一种主要木脂素,具有抗癌特性。然而,其对宫颈癌的抗癌作用尚未得到研究。在这里,我们研究了芝麻素对宫颈癌(HeLa)细胞系的影响,并探讨了其潜在的机制。

方法

用芝麻素培养 HeLa 细胞。用 CCK-8 法和划痕实验检测细胞增殖和迁移能力,用流式细胞术和 TUNEL 染色检测细胞凋亡,用 Western blot 检测 Bax 和 Bcl-2 的表达。用透射电子显微镜(TEM)进一步观察超微结构,检测 caspase-12、GRP78、GADD153、IRE1α、p-IRE1α、JNK、p-JNK、LC3I/II 和 beclin-1 的表达。此外,用 3-MA(自噬抑制剂)和/或芝麻素处理 HeLa 细胞,然后检测 LC3I/II 的表达和细胞活力。

主要发现

CCK-8 法和划痕实验表明芝麻素抑制 HeLa 细胞的增殖和迁移,而流式细胞术和 TUNEL 染色表明芝麻素诱导这些细胞凋亡。与对照组相比,芝麻素组 Bax、caspase-12、GRP78、GADD153、p-IRE1α、p-JNK、LC3I/II 和 beclin-1 的表达上调,而 Bcl-2 的表达下调。进一步的研究表明,芝麻素还诱导 HeLa 细胞自噬,抑制自噬增加芝麻素处理的 HeLa 细胞的活力。

意义

芝麻素通过 IRE1α/JNK 通路抑制 HeLa 细胞的增殖/迁移,并诱导内质网应激介导的细胞凋亡,同时激活这些细胞的自噬和自噬性死亡,进一步验证了芝麻素的抗癌作用。

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