title: Dihydroartemisinin Sensitizes Human Lung Adenocarcinoma A549 Cells to Arsenic Trioxide via Apoptosis.
abstract: Recent studies have shown that arsenic trioxide (ATO) is an effective anti-cancer drug for treatment of acute promyelocytic leukemia and other types of human cancer. However, we have found that lung cancer cells constantly develop a high level of resistance to ATO. In this study, we have explored a possibility of combination of dihydroartemisinin (DHA) and ATO treatments to reduce ATO resistance of lung cancer cells. We determined the combinatory effects of DHA and ATO on cytotoxicity of human lung adenocarcinoma (A549) cells. We showed that co-exposure to DHA and ATO of A549 cells synergistically increased the cytotoxicity and apoptotic cell death in the cells. We found that the synergistic effect of DHA and ATO in promoting apoptosis mainly resulted from increased cellular level of reactive oxygen species (ROS) and DNA damage. ATO alone only exerted moderate growth inhibitory effects on A549 cells. The results indicate that DHA can significantly sensitize ATO-induced cytotoxicity of A549 lung cancer cells through apoptosis mediated by ROS-induced DNA damage. Interestingly, we found that the combinatory treatment of DHA and ATO did not result in significant adverse effects in normal human bronchial epithelial (HBE) cells. Our results further provide evidence for the potential application of combinatory effects of DHA and ATO as a safe therapy for human lung cancer.
authors.affiliation: Department of Environmental Health and Occupational Medicine, West China School of Public Health, Sichuan University, No. 16, Section 3, Renmin Nan Road, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Environmental Health and Occupational Medicine, West China School of Public Health, Sichuan University, No. 16, Section 3, Renmin Nan Road, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Shiyan
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Environmental Health and Occupational Medicine, West China School of Public Health, Sichuan University, No. 16, Section 3, Renmin Nan Road, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Huangmei
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Environmental Health and Occupational Medicine, West China School of Public Health, Sichuan University, No. 16, Section 3, Renmin Nan Road, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Environmental Health and Occupational Medicine, West China School of Public Health, Sichuan University, No. 16, Section 3, Renmin Nan Road, Chengdu, 610041, Sichuan, People's Republic of China. zhangzunzhen@163.com.
authors.forename: Zunzhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival; D004249:DNA Damage / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001152:Arsenicals; D037621:Artemisinins; D010087:Oxides; D017382:Reactive Oxygen Species; C039060:artenimol; D000077237:Arsenic Trioxide
keywords: Apoptosis; Arsenic trioxide; Dihydroartemisinin; Drug resistance; Lung cancer cells