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

  • Environ Toxicol Pharmacol. 2021 Oct:87:103686. doi: 10.1016/j.etap.2021.103686.
Jie Tang  1 ,  Mingrong Bei  2 ,  Jia Zhu  3 ,  Guangtao Xu  3 ,  Deqing Chen  3 ,  Xin Jin  3 ,  Jianzhong Huang  4 ,  Jingjian Dong  5 ,  Lili Shi  5 ,  Long Xu  6 ,  Bo Hu  7
Affiliations
  • 1. Department of Pathology, and the Key-Innovative Discipline of Molecular Diagnostics, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, 314001, ZJ, China.
  • 2. Department of Cell Biology and Genetics, Shantou University College of Medicine, Shantou, 515041, GD, China.
  • 3. Forensic and Pathology Laboratory, Jiaxing University Medical College, Jiaxing, 314001, ZJ, China.
  • 4. Department of Public Health, Forensic and Pathology Laboratory, Jiaxing University Medical College, Jiaxing, 314001, ZJ, China.
  • 5. Medical Laboratory Center, Jiaxing University Medical College, Jiaxing, 314001, ZJ, China.
  • 6. Department of Public Health, Forensic and Pathology Laboratory, Jiaxing University Medical College, Jiaxing, 314001, ZJ, China. Electronic address: [email protected].
  • 7. Department of Pathology, and the Key-Innovative Discipline of Molecular Diagnostics, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, 314001, ZJ, China. Electronic address: [email protected].
PMID: 34098069 DOI: 10.1016/j.etap.2021.103686
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.

Keywords
Cadmium; GSDME; MDA-MB-231cells; NLRP3 inflammasome; Pyroptosis; ROS.
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