title: Tanshinone IIA exerts antitumor activity against vestibular schwannoma cells by inhibiting the expression of hypoxia-inducible factor-1α.
abstract: The aim of the present study was to evaluate the effect of the herbal medicine, tanshinone IIA (Tan IIA), on vestibular schwannoma (VS) cells and assess the functional targets of Tan IIA. HEI‑193 cells and Nf2‑/‑mouse Schwann (SC4) cells were used to investigate the inhibitory effects of Tan IIA on VS. Cell viability was measured using an MTT assay and apoptosis was assessed by flow cytometry. Western blot analysis and reverse transcription quantitative polymerase chain reaction (RT‑qPCR) were performed to assess the expression of hypoxia‑inducible factor‑1α (HIF‑1α) and its signaling pathways. In addition, the effect of Tan IIA on HIF‑1α transcription was determined using a luciferase reporter assay. Schwannoma cell proliferation was observed to be inhibited as the Tan IIA concentration increased under normoxic and hypoxic conditions. Furthermore, Tan IIA induced apoptosis in the HEI‑193 cells and inhibited the protein expression of HIF‑1α in the HEI‑193 cells under hypoxia, thus repressing the transcriptional activity of HIF‑1α. The present study demonstrated that HIF‑1α is expressed in hypoxic VS cells and Tan IIA inhibits VS cells by suppressing the activity of HIF‑1α. In conclusion, these results indicate that Tan IIA is a potential chemotherapeutic agent for the treatment of VS.
authors.affiliation: Department of Otorhinolaryngology ‑ Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon‑si, Gyeonggi‑do 420‑767, Republic of Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology ‑ Head and Neck Surgery, Korea University College of Medicine, Seoul 158‑867, Republic of Korea.
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Song
authors.affiliation: Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 300‑718, Republic of Korea.
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
authors.affiliation: Department of Otorhinolaryngology ‑ Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon‑si, Gyeonggi‑do 420‑767, Republic of Korea.
authors.forename: Jong Dae
authors.initials: JD
authors.lastname: Lee
mesh_terms: D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity; D010936:Plant Extracts / Q000737:chemistry; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; C021751:tanshinone; D008156:Luciferases