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Acute cadmium exposure induces GSDME-mediated pyroptosis in triple-negative breast cancer cells through ROS generation and NLRP3 inflammasome pathway activation.

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.
AuthorsJie Tang, Mingrong Bei, Jia Zhu, Guangtao Xu, Deqing Chen, Xin Jin, Jianzhong Huang, Jingjian Dong, Lili Shi, Long Xu, Bo Hu
JournalEnvironmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 87 Pg. 103686 (Oct 2021) ISSN: 1872-7077 [Electronic] Netherlands
PMID34098069 (Publication Type: Journal Article)
CopyrightCopyright © 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
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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