Molecular mechanism of inhibition of 8-gingerol on proliferation of breast cancer cells

Chong YANG; Ruoqiu FU; Ning GAO

doi:10.16016/j.1000-5404.201809200

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Molecular mechanism of inhibition of 8-gingerol on proliferation of breast cancer cells

Basic Medicine | 更新时间：2026-01-09

- Molecular mechanism of inhibition of 8-gingerol on proliferation of breast cancer cells
- Journal of Third Military Medical University Vol. 41, Issue 5, Pages: 406-414(2019)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系生药学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(31571425)
- DOI：10.16016/j.1000-5404.201809200
  CLC： R285.5;R73-36;R737.9
- Received：28 September 2018，
  
  Revised：2018-12-11，
  
  Published：15 March 2019
- 稿件说明：
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Chong YANG, Ruoqiu FU, Ning GAO. Molecular mechanism of inhibition of 8-gingerol on proliferation of breast cancer cells[J]. Journal of Third Military Medical University, 2019, 41(5): 406-414.
DOI：

Chong YANG, Ruoqiu FU, Ning GAO. Molecular mechanism of inhibition of 8-gingerol on proliferation of breast cancer cells[J]. Journal of Third Military Medical University, 2019, 41(5): 406-414. DOI： 10.16016/j.1000-5404.201809200.

摘要

目的

探讨8-姜酚抑制乳腺癌细胞增殖的分子机制。

方法

MTT法测定乳腺癌细胞MDA-MB-231细胞活性；流式细胞仪检测产生活性氧(reactive oxygen species

ROS)的细胞比例、细胞周期以及细胞凋亡；Western blot检测周期相关蛋白Cyclin D1和p-DCD2的表达。

结果

8-姜酚能明显抑制乳腺癌MDA-MB-231和MCF-7细胞的增殖活性，差异有统计学意义(

0.01)，72 h的IC

值分别为(22.06±2.93)、(35.77±5.96)μmol/L；流式细胞仪检测结果发现8-姜酚可导致乳腺癌细胞G

期阻滞，诱导细胞产生ROS；8-姜酚作用于MDA-MB-231和MCF-7细胞24 h后G

期细胞的百分比分别为(69.23±3.77)%、(65.87±3.76)%，与对照组G

期的细胞比例(47.39±1.97)%、(49.17±3.52)%相比，差异具有统计学意义(

0.01)；用NAC抑制ROS后减弱了8-姜酚对乳腺癌细胞G

期的阻滞作用，用P38抑制剂抑制P38蛋白磷酸化水平后也减弱了8-姜酚对乳腺癌细胞G

期的阻滞作用。Western blot结果显示8-姜酚可以上调MAPK信号通路中P38蛋白的磷酸化水平；并可下调G

期相关蛋白Cyclin D1和p-CDC2的表达，用NAC抑制ROS后减弱了8-姜酚对P38磷酸化水平上调作用的同时还减弱了8-姜酚对周期相关蛋白CyclinD1、p-CDC2的下调作用；用P38抑制剂抑制P38蛋白磷酸化水平后同样减弱了8-姜酚对周期相关蛋白CyclinD1、p-CDC2的下调作用。

结论

8-姜酚具有明显的抑制肿瘤增殖活性的作用，其作用机制可能为8-姜酚通过诱导乳腺癌细胞产生ROS从而导致MAPK信号通路中P38的磷酸化激活，进而引起乳腺癌细胞的周期阻滞。

Abstract

Objective

To investigate the effect of cell cycle on breast cancer cells by 8-gingerol.

Methods

The cell viability of breast cancer cells MDA-MB-231 and MCF-7 after treated by 8-gingerol at the doses of 0

30 or 40 μmol/L for 24

48 or 72 h was assessed by MTT assay. The cell cycle

apoptosis and proportion of cells producing ROS were measured by flow cytometry. The expression of cell cycle associated proteins

Cyclin D1 and p-CDC2 were detected by Western blot analysis.

Results

8-gingerol evidently inhibited the proliferation of breast cancer MDA-MB-231 and MCF-7 cells (

0.01). The inhibitory concentration of IC

were 22.06±2.93 and 35.77±5.96 μmol/

respectively in the breast cancer MDA-MB-231 and MCF-7 cells after 72 h treatment with 8-gingerol. The results of flow cytometry showed that 8-gingerol can cause G

phase arrest and induce cells to produce ROS in the breast cancer MDA-MB-231 and MCF-7 cells after treatment with 8-gingerol for 72 h. Flow cytometry found that 8-gingerol resulted in cell cycle arrest at G

phase cells was (69.23±3.77)% and (65.87±3.76)%

respectively in the MDA-MB-231 and MCF-7 cells after 8-gingerol treatment for 24 h

significantly higher than in the cells without treatment [(47.39±1.97)%

(49.17±3.52)%

0.01

]

. Pretreatment with NAC weakened the effect of 8-gingerol on G

phase arrest. Western blot results showed that 8-gingerol resulted in the decreases of Cyclin D1 and p-CDC2 levels

and upregulated the phosphorylation level of P38. The inhibition of ROS by NAC attenuated the up-regulation of phosphorylation of P38 by 8-gingerol and the down-regulation of cyclin-related proteins Cyclin D1 and p-CDC2. The inhibition of P38 phosphorylation by P38 inhibitors also attenuated the down-regulation of cyclin-associated proteins Cyclin D1 and p-CDC2 by 8-gingerol.

Conclusion

8-gingerol exhibits obviously inhibitory effects on breast cancer cell proliferation. The mechanism may be that 8-gingerol induces ROS in breast cancer cells

which leads to phosphorylation of P38 in the MAPK signaling pathway

and then leads to cell cycle arrest.

关键词

Keywords

references

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