1. Acute cadmium exposure induces GSDME-mediated pyroptosis in triple-negative breast cancer cells through ROS generation and NLRP3 inflammasome pathway activation.
- Author
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Tang J, Bei M, Zhu J, Xu G, Chen D, Jin X, Huang J, Dong J, Shi L, Xu L, and Hu B
- Subjects
- Caspase 3 metabolism, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Humans, Pyroptosis drug effects, Signal Transduction drug effects, Cadmium toxicity, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Reactive Oxygen Species metabolism, Receptors, Estrogen metabolism, Triple Negative Breast Neoplasms metabolism
- 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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