Back to Search
Start Over
Thymoquinone inhibits cell proliferation, migration, and invasion by regulating the elongation factor 2 kinase (eEF-2K) signaling axis in triple-negative breast cancer
- Source :
- Breast cancer research and treatment. 171(3)
- Publication Year :
- 2017
-
Abstract
- Triple-negative breast cancer (TNBC) is the most aggressive and chemoresistant subtype of breast cancer. Therefore, new molecular targets and treatments need to be developed to improve poor patient prognosis and survival. We have previously shown that eukaryotic elongation factor 2 kinase (eEF-2K) is highly expressed in TNBC cells, is associated with poor patient survival and prognosis, and promotes cell proliferation, migration, and invasion. In vivo targeting of eEF-2K significantly reduces the tumor growth of orthotopic TNBC xenograft mouse models, suggesting that eEF-2K may serve as a potential novel therapeutic target. In the current study, we identified thymoquinone (TQ), an active ingredient of Nigella sativa, as a potential safe and effective eEF-2K inhibitor in TNBC. We demonstrated for the first time that TQ inhibits the protein and mRNA expression of eEF-2K, as well as the clinically relevant downstream targets, including Src/FAK and Akt, and induces the tumor suppressor miR-603, in response to NF-kB inhibition. This effect was associated with a significant decrease in the proliferation, colony formation, migration, and invasion of TNBC cells. Furthermore, systemic in vivo injection of TQ (20 and 100 mg/kg) significantly reduced the growth of MDA-MB-231 tumors and inhibited the eEF-2K expression in an orthotopic tumor model in mice. Our study provides first evidence that TQ treatment inhibits cell proliferation, migration/invasion, and tumor growth, in part through the inhibition of eEF-2K signaling in TNBC. Thus, our findings suggest that systemic TQ treatment may be used as a targeted therapeutic strategy for the inhibition of eEF-2K in TNBC tumor growth and progression.
- Subjects :
- 0301 basic medicine
Elongation Factor 2 Kinase
Cancer Research
Triple Negative Breast Neoplasms
Biology
law.invention
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Breast cancer
In vivo
law
Cell Movement
Cell Line, Tumor
medicine
Benzoquinones
Animals
Humans
Neoplasm Invasiveness
RNA, Messenger
Protein kinase B
Thymoquinone
Triple-negative breast cancer
Cell Proliferation
Cell growth
medicine.disease
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer research
Suppressor
Female
Proto-oncogene tyrosine-protein kinase Src
Signal Transduction
Subjects
Details
- ISSN :
- 15737217
- Volume :
- 171
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Breast cancer research and treatment
- Accession number :
- edsair.doi.dedup.....0e1dae042db1d2ec81de4df01befffff