Abstract |
Cadmium (Cd) exposure can exert an impact on carcinogenicity of breast cancer, however, the mechanism is not fully understood in triple-negative breast cancer (TNBC). We performed a TNBC MDA-MB-231 cell model and assessed the toxic effect of Cd exposure (0, 10, 20, 50, 60, 80 μM). Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Lactate dehydrogenase (LDH) release, apoptosis and pyroptosis were increased, which were relieved by z-VAD. Elevated ROS and NLRP3, caspase-1, IL-1β and IL-18 were detected, which was attenuated by N-acetylcysteine. Increased bax and decreased caspase-8, caspase-9 and caspase-3 were found. gasdermin E (GSDME) was activated with cleavage of GSDME-NT, which was retarded by z-VAD. Additionally, p38 MAPK signaling pathway was activated. Our data demonstrate GSDME-activated pyroptosis in Cd toxicity, implying a potential impact on TNBC.
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Authors | Jie Tang, Mingrong Bei, Jia Zhu, Guangtao Xu, Deqing Chen, Xin Jin, Jianzhong Huang, Jingjian Dong, Lili Shi, Long Xu, Bo Hu |
Journal | Environmental toxicology and pharmacology
(Environ Toxicol Pharmacol)
Vol. 87
Pg. 103686
(Oct 2021)
ISSN: 1872-7077 [Electronic] Netherlands |
PMID | 34098069
(Publication Type: Journal Article)
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Copyright | Copyright © 2021 Elsevier B.V. All rights reserved. |
Chemical References |
- GSDME protein, human
- Inflammasomes
- NLR Family, Pyrin Domain-Containing 3 Protein
- NLRP3 protein, human
- Reactive Oxygen Species
- Receptors, Estrogen
- Cadmium
- CASP3 protein, human
- Caspase 3
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Topics |
- Cadmium
(toxicity)
- Caspase 3
(metabolism)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Humans
- Inflammasomes
(metabolism)
- NLR Family, Pyrin Domain-Containing 3 Protein
(metabolism)
- Pyroptosis
(drug effects)
- Reactive Oxygen Species
(metabolism)
- Receptors, Estrogen
(metabolism)
- Signal Transduction
(drug effects)
- Triple Negative Breast Neoplasms
(metabolism)
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