title: Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells.
abstract: Medullary thyroid carcinoma (MTC) originates from the C‑cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC‑SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription‑quantitative polymerase chain reaction of nuclear factor‑κB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC‑bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC‑SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC‑mice, and no change in the expression of NEMO was detected in the treated MTC‑SK cells. The observation of early‑onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti‑apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC‑SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway.
authors.affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.
authors.forename: Victor
authors.initials: V
authors.lastname: Aguiriano-Moser
authors.affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Svejda
authors.affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.
authors.forename: Zeng-Xia
authors.initials: ZX
authors.lastname: Li
authors.affiliation: Department of Pharmacognosy, Institute of Pharmacy, Center of Molecular Biosciences, Leopold Franzens University of Innsbruck, Innsbruck A‑6010, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sturm
authors.affiliation: Department of Pharmacognosy, Institute of Pharmacy, Center of Molecular Biosciences, Leopold Franzens University of Innsbruck, Innsbruck A‑6010, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.affiliation: Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Himberg A‑2325, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ingolic
authors.affiliation: Research Institute for Electron Microscopy and Fine Structure Research, University of Technology Graz, Graz A‑8010, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Höger
authors.affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Siegl
authors.affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meier-Allard
authors.affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.
authors.forename: Anton
authors.initials: A
authors.lastname: Sadjak
authors.affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Pfragner
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018703:Founder Effect; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D010936:Plant Extracts / Q000737:chemistry; D019666:Rubiaceae / Q000737:chemistry*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053181:Caspase 8; D051550:I-kappa B Kinase; D010936:Plant Extracts; D014315:Triterpenes; D000097245:Ursolic Acid; C491731:IKBKG protein, human