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Ketamine suppresses proliferation and induces ferroptosis and apoptosis of breast cancer cells by targeting KAT5/GPX4 axis
- Source :
- Biochemical and biophysical research communications. 585
- Publication Year :
- 2021
-
Abstract
- Breast cancer (BC) serves as a prevalent and mortal malignancy among female globally. Ferroptosis, as an oxidative cell death that characterized by abnormal iron accumulation, plays critical role in cancer development. Ketamine is a rapid-acting anesthetic agent and has presented potential anti-tumor properties. However, the effect of Ketamine on breast cancer is still obscure. Here, we aimed to explore the function of Ketamine in the modulation of proliferation and ferroptosis of breast cancer cells. The cell viability of breast cancer cells was repressed by the treatment of Ketamine, while ferroptosis inhibitor ferrostatin 1 and apoptosis inhibitor ZVAD-FMK could restore the cell viability. The treatment of Ketamine significantly decreased the Edu-positive breast cancer cells and the colony formation numbers, and the treatment of ferrostatin 1 reversed the effect of Ketamine. We observed that the levels of ferroptosis markers, such as MDA, lipid ROS, and Fe2+ were increased by the treatment of Ketamine in breast cancer cells. Regarding to the mechanism, we found that Ketamine inhibited the expression of GPX4, an anti-ferroptosis factor, by attenuating KAT5 on the promoter region of GPX4, repressing the enrichment of histone H3 lysine 27 acetylation (H3K27ac) and RNA polymerase II (RNA pol II). The treatment of Ketamine reduced the cell viability and proliferation of breast cancer cells, in which the overexpression of KAT5 or GPX4 was able to restore the phenotypes. The treatment of Ketamine induced the levels of MDA, lipid ROS, and Fe2+, while KAT5 or GPX4 overexpression could reverse this effect in breast cancer cells. Thus, we concluded that Ketamine suppressed proliferation and induced ferroptosis of breast cancer cells by targeting KAT5/GPX4 axis. Ketamine may serve as a potential therapeutic strategy for breast cancer.
- Subjects :
- Programmed cell death
Apoptosis Inhibitor
Cell Survival
Biophysics
Apoptosis
Breast Neoplasms
GPX4
Biochemistry
Lysine Acetyltransferase 5
Histone H3
Breast cancer
Cell Line, Tumor
Medicine
Ferroptosis
Humans
Viability assay
skin and connective tissue diseases
KAT5
Molecular Biology
Anesthetics
Cell Proliferation
business.industry
Reverse Transcriptase Polymerase Chain Reaction
Cell Biology
medicine.disease
Phospholipid Hydroperoxide Glutathione Peroxidase
Gene Expression Regulation, Neoplastic
Cancer research
MCF-7 Cells
Female
Ketamine
business
Signal Transduction
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 585
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....3f4fa1269af08a1471e1cd8fd7f531cd