Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway.
Yujiao ZhangYizeng FanShangke HuangGuanying WangRui HanFuxi LeiAnqi LuoXin JingLin ZhaoShanzhi GuXinhan ZhaoPublished in: Cancer science (2018)
Thymoquinone (TQ, 2-methyl-5-isopropyl-1,4-benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti-tumor efficiency in various cancers. Autophagy is a self-digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786-O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ-treated RCC cells, and then found that autophagy was induced by TQ in 786-O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy-dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ-induced autophagy in RCC treatment.
Keyphrases
- induced apoptosis
- signaling pathway
- endoplasmic reticulum stress
- cell death
- cell cycle arrest
- pi k akt
- oxidative stress
- renal cell carcinoma
- epithelial mesenchymal transition
- cell proliferation
- skeletal muscle
- small cell lung cancer
- cell therapy
- single cell
- mass spectrometry
- young adults
- protein kinase
- drug induced
- atomic force microscopy
- binding protein
- mesenchymal stem cells