title: Artesunate induces apoptosis and inhibits growth of Eca109 and Ec9706 human esophageal cancer cell lines in vitro and in vivo.
abstract: Esophageal cancer is a common malignant tumor worldwide with a high incidence rate in China and it is a great threat to human health. Combined modality therapy is used for chemotherapeutic treatment of esophageal cancer; however, drug resistance and side effects of the drugs is a major barrier to the success of chemotherapy. As chemotherapy with common drugs is far from providing satisfactory clinical outcomes for patients with esophageal cancer, more efficient drugs are urgently required. Artesunate (Art) is the first-line treatment option for malaria; however, it was recently revealed that Art has remarkable anti-tumor activity, making it a novel candidate for cancer chemotherapy. Although the anti-cancer effects of Art have been well documented, its potential against esophageal cancer has rarely been explored. The present study aimed to investigate the significance and mechanism of the anti-proliferative activity of Art on esophageal cancer cells in vitro and in vivo. In the in vitro experiments, Art inhibited the growth as well as induced cell apoptosis and cell cycle arrest of esophageal cancer cell lines (Eca109 and Ec9706) in a concentration-dependent manner. Furthermore, downregulation of mitochondrial membrane potential, B-cell lymphoma-2 (BCL-2) and CDC25A, as well as upregulation of BCL-2‑associated X protein (Bax) and caspase-3 expression in Art-treated cells were identified. In addition, an in vivo study showed that Art produced a dose-dependent tumor regression in nude mice, while side effects were low. The anti-tumor activity of 200 mg/kg Art was similar to that of 3 mg/kg cisplatin. In conclusion, Art exerted concentration-dependent inhibitory activity against esophageal cancer in vivo and in vitro by inducing cell apoptosis and cell cycle arrest through affecting mitochondrial membrane potential, BCL-2, Bax, caspase-3 and CDC25A.
authors: Department of FCM Analysis, Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors: Liang
authors: L
authors: Liu
authors: Department of FCM Analysis, Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors: Lian-Fu
authors: LF
authors: Zuo
authors: Department of FCM Analysis, Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors: Jing
authors: J
authors: Zuo
authors: Department of FCM Analysis, Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors: Jing
authors: J
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D020687:cdc25 Phosphatases / Q000096:biosynthesis
chemical_list: D037621:Artemisinins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000077332:Artesunate; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D053148:Caspase 3; D002945:Cisplatin