Sinapine induced ferroptosis in non-small cell lung cancer cells by upregulating transferrin/transferrin receptor and downregulating SLC7A11. 2022

Min Shao, and Qi Jiang, and Chao Shen, and Zhong Liu, and Lihong Qiu
Health Management Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Sinapine (SI) is a naturally occurring product with biological properties, but its activity against non-small cell lung cancer (NSCLC) remains unclear. This research examined the anti-tumour effects of SI in NSCLC cells and the underlying mechanisms of any effects. SI induced ferroptosis, a novel form of cell death, by increasing intracellular ferrous iron, lipid peroxidation, and reactive oxygen species (ROS) in NSCLC cells. SI treatment resulted in transferrin and transferrin receptor upregulation, and inhibition of transferrin or the transferrin receptor reduced the ferroptosis caused by SI. SI treatment also resulted in a p-53 dependent downregulation of SLC7A11. Finally, we evaluated the effects of SI in vivo and it was found that SI also successfully inhibited the growth of NSCLC in vivo. In summary, our data demonstrated that SI triggered ferroptosis in NSCLC cells and may be a promising therapeutic agent for this condition.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D011990 Receptors, Transferrin Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released. Transferrin Receptors,Transferrin Receptor,Receptor, Transferrin
D002289 Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D002794 Choline A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000079403 Ferroptosis A form of REGULATED CELL DEATH initiated by oxidative perturbations of the intracellular microenvironment that is under constitutive control by glutathione peroxidase 4 and can be inhibited by iron chelators and lipophilic antioxidants. Oxytosis
D014168 Transferrin An iron-binding beta1-globulin that is synthesized in the LIVER and secreted into the blood. It plays a central role in the transport of IRON throughout the circulation. A variety of transferrin isoforms exist in humans, including some that are considered markers for specific disease states. Siderophilin,Isotransferrin,Monoferric Transferrins,Serotransferrin,Transferrin B,Transferrin C,beta 2-Transferrin,beta-1 Metal-Binding Globulin,tau-Transferrin,Globulin, beta-1 Metal-Binding,Metal-Binding Globulin, beta-1,Transferrins, Monoferric,beta 1 Metal Binding Globulin,beta 2 Transferrin,tau Transferrin
D027182 Amino Acid Transport System y+ A sodium-independent, basic amino acid transport system with a high-affinity for LYSINE; ARGININE; and ORNITHINE. Amino Acid Transport System y-Plus,System y+ Transporter,Amino Acid Transport System y Plus,Transporter, System y+,y+ Transporter, System

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