Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway.
10.1007/s11655-024-4104-y
- Author:
Dan HE
1
;
Xiao-Ning TAN
2
;
Lin-Pei LI
3
;
Wen-Hui GAO
4
;
Xue-Fei TIAN
5
;
Pu-Hua ZENG
6
,
7
Author Information
1. Hunan Academy of Chinese Medicine, Changsha, 410006, China.
2. Scientific Research Department, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, 410006, China.
3. Oncology Department, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, 410006, China.
4. School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China.
5. School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China. 003640@hnucm.edu.cn.
6. Hunan Academy of Chinese Medicine, Changsha, 410006, China. zph120@
7. com.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
brazilin;
breast cancer;
ferroptosis;
p53/SLC7A11/GPX4 axis
- MeSH:
Ferroptosis/drug effects*;
Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism*;
Breast Neoplasms/drug therapy*;
Signal Transduction/drug effects*;
Female;
Cell Line, Tumor;
Tumor Suppressor Protein p53/metabolism*;
Amino Acid Transport System y+/metabolism*;
Humans;
Reactive Oxygen Species/metabolism*;
Animals;
Mice;
Cell Proliferation/drug effects*;
Mitochondria/metabolism*;
Coenzyme A Ligases/metabolism*;
Cell Movement/drug effects*;
Benzopyrans
- From:
Chinese journal of integrative medicine
2024;30(11):1001-1006
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells.
METHODS:Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay.
RESULTS:Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05).
CONCLUSIONS:Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.
