title: Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells.
abstract: Head and neck cancer is the sixth most common cancer worldwide. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, exhibits a wide range of biological roles including a highly efficient and specific anti-tumor activity. Here, we aimed to examine the effect of DHA on head and neck carcinoma cells and elucidate the potential mechanisms. We used five head and neck carcinoma cell lines and two non-tumorigenic normal epithelial cell lines to achieve our goals. Cells were exposed to DHA and subjected to cellular activity assays including viability, cell cycle analysis, cell death, and angiogenic phenotype. Our results show that DHA causes cell cycle arrest which is mediated through Forkhead box protein M1 (FOXM1). We also demonstrate that DHA induces ferroptosis and apoptosis in head and neck carcinoma cells. Lastly, our results show that DHA alters the angiogenic phenotype of cancer cells by reducing the expression of angiogenic factors and the ability of cancer cells to support endothelial cell tubule formation. Our study suggests that DHA specifically causes head and neck cancer cell death through contribution from both ferroptosis and apoptosis. DHA may represent an effective strategy in head and neck cancer treatment.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Renyu
authors.initials: R
authors.lastname: Lin
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Feng
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: wzmuwangli@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China. Electronic address: wzmcliangguang@163.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D042501:Angiogenic Proteins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D037621:Artemisinins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C039060:artenimol
keywords: Antitumor; Cell cycle; Dihydroartemisinin; Ferroptosis; Head and neck cancer