Bufalin Induces Programmed Necroptosis in Triple-Negative Breast Cancer Drug-Resistant Cell Lines through RIP1/ROS-Mediated Pathway.
10.1007/s11655-021-3458-7
- Author:
Xiao-Dan LIU
1
;
Cheng-Yang SONG
2
;
Cui-Cui KONG
3
;
Xin TIAN
4
Author Information
1. Department of Breast Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China.
2. Department of Thoracic Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China.
3. Molecular Oncology Laboratory of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
4. Molecular Oncology Laboratory of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China. tianxin@cmu1h.com.
- Publication Type:Journal Article
- Keywords:
bufalin;
drug resistant;
necroptosis;
reactive oxygen species pathway;
triple-negative breast cancer
- MeSH:
Antioxidants/pharmacology*;
Apoptosis;
Bufanolides;
Caspase 3/metabolism*;
Cell Line;
Cell Line, Tumor;
Cysteine/pharmacology*;
Docetaxel/pharmacology*;
Doxorubicin/pharmacology*;
Fluorescein-5-isothiocyanate/pharmacology*;
Humans;
Necroptosis;
Propidium/pharmacology*;
Reactive Oxygen Species/metabolism*;
Receptors, Tumor Necrosis Factor;
Triple Negative Breast Neoplasms/drug therapy*;
Tumor Necrosis Factor-alpha/pharmacology*
- From:
Chinese journal of integrative medicine
2022;28(10):900-908
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To explore the effect and mechanism of action of bufalin in triple-negative breast cancer (TNBC) drug-resistant cell lines.
METHODS:The normal human mammary epithelial cell line, TNBC cell line, TNBC adriamycin-resistant cell line, and TNBC docetaxel-resistant cell line were treated with different doses of bufalin (0-1,000 nmol/L) at different time points (0-72 h). Propidium iodide staining, AV-FITC/PI double staining, Hoechst 33342/PI double staining and transmission electron microscopy (TEM) were used to evaluate the death patterns of the cell lines.
RESULTS:Bufalin killed the TNBC cell line and its drug-resistant cell lines in a dose/time-dependent manner (all P<0.01). After treatment with bufalin for 24 h, the adriamycin-resistant cell line showed a co-existing pattern of necroptosis and apoptosis. However, at 48 h, necroptosis was the main manifestation. After treatment with bufalin, the expressions of tumor necrosis factor α, phospho-tumor necrosis factor receptor 1, phospho-receptor interacting protein 1 and c-caspase 3 increased (all P<0.01), the killing effect of bufalin could be mostly inhibited by NEC-1, and by z-VAD-fmk (both P<0.01). Besides, the intracellular reactive oxygen species (ROS) levels increased considerably (P<0.01), the antioxidant N-acetyl cysteine or Nec-1 could inhibit the increase of ROS level and the killing effect of bufalin (all P<0.01). The adriamycin-resistant cell line exhibited necroptosis characteristic after 48 h of bufalin treatment under TEM.
CONCLUSIONS:Bufalin could induce necroptosis through RIP1/ROS-mediated pathway to kill the drug-resistant TNBC cell lines. This finding provides critical experimental data and theoretical basis for the clinical application of bufalin to overcome the difficulties in the treatment of TNBC.
