title: Arsenic Trioxide and Icariin Show Synergistic Anti-leukemic Activity.
abstract: Although As2O3 (ATO) has been recommended as the front-line agent for treatment of acute promyelocytic leukemia (APL), particularly for relapsed or refractory APL, it has been associated with profound toxicity. Icariin is a natural compound with activity against a variety of cancers. This study was designed to investigate the effect of Icariin on APL cells and to determine whether Icariin can potentiate the antitumor activity of ATO in APL cells. Cell proliferation and apoptosis were measured using MTT assay and flow cytometry, respectively. The expression of apoptosis and proliferation-related molecules was detected by Western blotting. Reactive oxygen species (ROS) and mitochondrial membrane potential were determined with florescence staining. Icariin inhibited proliferation in a dose-dependent manner and induced apoptosis in both of the tested APL cell lines. Icariin enhanced the in vitro antitumor activity of ATO against APL. The antitumor activity of Icariin and its enhancement of the antitumor activity of ATO correlated with the increase in accumulation of intracellular ROS. Our results showed that Icariin, by increasing intracellular ROS, exhibited antitumor activity and potentiated the antitumor activity of ATO against APL. Therefore, combination treatment with Icariin and ATO might offer a novel therapeutic option for patients with APL, although further studies are needed.
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Medical College Qingdao University, Qingdao, 266003, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Medical College Qingdao University, Qingdao, 266003, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Medical College Qingdao University, Qingdao, 266003, China. drlilingdai@sina.com.
authors.forename: Liling
authors.initials: L
authors.lastname: Dai
authors.affiliation: Emergency Department of Qingdao Emergency Center, Qingdao, 266035, China.
authors.forename: Tongguo
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Medical College Qingdao University, Qingdao, 266003, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Medical College Qingdao University, Qingdao, 266003, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Medical College Qingdao University, Qingdao, 266003, China.
authors.forename: Luning
authors.initials: L
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D005419:Flavonoids; D010087:Oxides; D017382:Reactive Oxygen Species; D000077237:Arsenic Trioxide; C056599:icariin
keywords: APL; ATO; Icariin; ROS; Synergistic effect