title: Artemisinin inhibits gallbladder cancer cell lines through triggering cell cycle arrest and apoptosis.
abstract: Primary gallbladder cancer (GBC) is the most common malignancy of the digestive system. Due to its resistance to standard chemotherapy, no effective treatments are available at present. Artemisinin, a plant-derived anti‑malarial drug, has recently been shown to have anti-proliferative effects on a range of human cancer cell types. However, the efficacy of artemisinin against gallbladder cancer has not been reported. The present study investigated the effects of artemisinin on the proliferation, cell cycle and apoptosis of gallbladder cancer cell lines. A cell viability assay and an in vivo xenograft study demonstrated that artemisinin significantly inhibited the growth of gallbladder cancer. Western blot analysis indicated that artemisinin induced the expression of p16, while down‑regulating phosphorylated extracellular signal‑regulated kinase (ERK)1/2, CDK4 and cyclin D1 expression, leading to inhibition of the ERK1/2 pathway. Furthermore, flow cytometry and western blot analysis showed that artemisinin caused G1-phase arrest of the cell cycle, promoted the generation of reactive oxygen species (ROS), led to a collapse of the mitochondrial membrane potential and to triggered cytochrome c release from the mitochondria into the cytoplasm, which finally activated caspase‑3‑mediated apoptosis. In conclusion, the present study demonstrated that artemisinin inhibits the proliferation of gallbladder cancer cells in vitro as well as in vivo and induces apoptosis via induction of ROS and cell cycle arrest. These results suggested that artemisinin may be suitable for the treatment of gallbladder cancer.
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233003, P.R. China.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Jia
authors.affiliation: Yancheng Institute of Health Sciences, Clinical Medical College, Yancheng, Jiangsu 224000, P.R. China.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233003, P.R. China.
authors.forename: Ligong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233003, P.R. China.
authors.forename: Chenxu
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233003, P.R. China.
authors.forename: Yaguo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233003, P.R. China.
authors.forename: Xicheng
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233003, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D037621:Artemisinins; D007783:Lactones; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; C075875:artemisin