title: Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase.
abstract: The resistance of non-small cell lung cancer (NSCLC) to radiation is the major reason for radiotherapy failure of this kind cancer. Currently, there is no effective radiosensitizer in clinical use. Artemisinin and its derivates enhance radiotherapeutic effect in some kinds of tumors; however, whether artemisinin and its derivates can enhance the radiosensitivity of NSCLC remains unknown. Therefore, in the present experiments, artemisinin and its derivatives were firstly screened for their radiosensitization on NSCLC A549 (A549) cells and then the possible mechanisms were investigated. Our results showed that artesunate enhance radiosensitivity of A549 cells in vitro among artemisinin and its derivatives, and artesunate combined with local radiotherapy retarded the tumor growth in nude tumor xenografts; the inhibition produced by 30 mg/kg of artesunate was 74.6%. The results on the possible mechanisms showed artesunate increased the NO level within irradiated A549 cells. Artesunate didn't induce apoptosis of irradiated cells but induced G(2)/M arrest. The induced G(2)/M arrest was related to down-regulated cyclin B1 mRNA expression. Taken together, artesunate exhibited potent radiosensitivity against human A549 cells in vitro and in vivo, probably via NO signal transduction pathway to induce cell cycle arrest at G(2)/M phase. Therefore, artesunate should be further investigated as a radiosensitizer in clinical application.
authors: Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, PR China.
authors: Yanyan
authors: Y
authors: Zhao
authors: Weiwei
authors: W
authors: Jiang
authors: Bin
authors: B
authors: Li
authors: Qi
authors: Q
authors: Yao
authors: Junqing
authors: J
authors: Dong
authors: Yanyan
authors: Y
authors: Cen
authors: Xichun
authors: X
authors: Pan
authors: Jun
authors: J
authors: Li
authors: Jiang
authors: J
authors: Zheng
authors: Xueli
authors: X
authors: Pang
authors: Hong
authors: H
authors: Zhou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D056744:Cyclin B1 / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D009569:Nitric Oxide / Q000096:biosynthesis*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D056744:Cyclin B1; D011838:Radiation-Sensitizing Agents; D009569:Nitric Oxide; D000077332:Artesunate