Department of Pathology, and the Key-Innovative Discipline of Molecular Diagnostics, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, 314001, ZJ, China.
Department of Cell Biology and Genetics, Shantou University College of Medicine, Shantou, 515041, GD, China.
Environ Toxicol Pharmacol. 2021 Oct;87:103686. doi: 10.1016/j.etap.2021.103686. Epub 2021 Jun 5.
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.
镉（Cd）暴露会对乳腺癌的致癌性产生影响，但在三阴性乳腺癌（TNBC）中其机制尚不完全清楚。我们构建了 TNBC MDA-MB-231 细胞模型，评估了 Cd 暴露（0、10、20、50、60、80 μM）的毒性作用。Cd 暴露呈时间和剂量依赖性降低细胞活力，随后 S 期细胞周期停滞，cyclin 1A1、cyclin 1D1 和 CDK2 发生改变。LDH 释放、细胞凋亡和焦亡增加，被 z-VAD 缓解。检测到 ROS 和 NLRP3、caspase-1、IL-1β 和 IL-18 升高，被 N-乙酰半胱氨酸减弱。发现 bax 增加，caspase-8、caspase-9 和 caspase-3 减少。GSDME-NT 被切割，GSDME 被激活，被 z-VAD 抑制。此外，p38 MAPK 信号通路被激活。我们的数据表明，Cd 毒性中 GSDME 激活的焦亡，暗示其对 TNBC 可能有潜在影响。
