title: Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells.
abstract: The anticancer effects of artesunate (ART) have been well documented. However, its potential against skin cancer has not been explored yet. Herein we reported that 60 μmol/l ART effectively inhibited A431 (human epidermoid carcinoma cells) growth but not that of HaCaT (normal human keratinocyte cells). Our results revealed that ART induced cell cycle arrest at G0/G1 phase through the downregulation of cyclin A1, cyclin B, cyclin D1, Cdk2, Cdk4, and Cdk6. This correlated with the upregulation of p21 and p27. The 5-bromodeoxyuridine incorporation assay also indicated that ART treatment reduced DNA synthesis in a time-dependent manner. Furthermore, ART induced mitochondrial apoptosis, as evidenced by annexin V/propidium iodide staining and western blot analysis. Interestingly, ART-induced apoptosis diminished under iron-deficient conditions but intensified under iron-overload conditions. Taken together, these findings demonstrated the potential of ART in treating skin cancer through the induction of G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis and supported further investigations in other test systems.
authors.affiliation: Department of Clinical Laboratory, Chengdu Military General Hospital, Chengdu Military District, Chengdu, China.
authors.forename: Zhongyong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Jin
authors.initials: J
authors.lastname: Chai
authors.forename: Henry Hon Fung
authors.initials: HH
authors.lastname: Chuang
authors.forename: Shifeng
authors.initials: S
authors.lastname: Li
authors.forename: Tianran
authors.initials: T
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.forename: Deshan
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D018797:Cell Cycle Proteins; D000077332:Artesunate; D007501:Iron; D053148:Caspase 3