title: Icariin synergizes with arsenic trioxide to suppress human hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is an aggressive malignancy with high chemoresistance to chemotherapeutics. Arsenic trioxide (ATO) is of therapeutic potential for the treatment of HCC; however, the therapeutic benefit of ATO is very limited due to narrow therapeutic window. Icariin is a natural compound which inhibits tumour cell growth and induces apoptotic cell death in a variety of cancer cells. This study was designed to determine whether Icariin can potentiate the antitumour activity of ATO in HCC treatment. Cell proliferation and apoptosis were measured using an MTT assay and flow cytometry respectively. Changes in reactive oxygen species (ROS) level and mitochondrial membrane potential were analysed by fluorescence signals. Protein expression was measured by western blotting and NF-κB activity was determined by ELISA assay. In addition, the antitumour effect of combination treatment with Icariin and ATO on HCC was evaluated using a murine HCC cancer xenograft model. Icariin inhibited proliferation and induced apoptosis in both of the tested HCC cell lines in a dose-dependent fashion. Icariin enhanced the antitumour activity of ATO both in vitro and in vivo. The antitumour activity of Icariin and its enhancement of the antitumour activity of ATO correlated with the generation of intracellular ROS and inhibition of NF-κB activity. Our results showed that Icariin potentiated the antitumour activity of ATO in HCC. Therefore, we propose that the combination treatment with Icariin and ATO might facilitate the optimization of ATO therapy for patients with HCC.
authors: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, 250021, Shandong, China.
authors: Wen
authors: W
authors: Li
authors: Min
authors: M
authors: Wang
authors: Lingyun
authors: L
authors: Wang
authors: Shusheng
authors: S
authors: Ji
authors: Junyong
authors: J
authors: Zhang
authors: Chunqing
authors: C
authors: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D005419:Flavonoids; D016328:NF-kappa B; D010087:Oxides; D017382:Reactive Oxygen Species; D000077237:Arsenic Trioxide; C056599:icariin