FRACTIONS FROM TRAILLIAEDOXA GRACILIS (WW SMITH & FOREST) INHIBIT TUMOR CELL GROWTH AND INDUCE APOPTOSIS IN MEDULLARY THYROID CARCINOMA CELLS

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Aguiriano Moser V.1, Svejda B.1, Siegl V.1, Hoger H.2, Sturm S.3, Stuppner H.3, Ingolic E.4, Pfragner R.1
1 Department of Pathophysiology & Immunology, Center of Molecular Medicine, Medical University of Graz, Graz, Austria; 2Core Unit of Biomedical Research, Division of Laboratory Animal Science & Genetics, Medical University of Vienna, Himberg, Austria; 31nstitute of Pharmacy/Pharmacognosy, Center of Molecular Biosciences, University of Innsbruck, Innsbruck, Austria; 4Research Institute for Electron Microscopy & Finestructure Research, Technical University of Graz, Austria
Background: Medullary thyroid carcinoma is a neuroendocrine tumor arising from the parafollicular C-cells of the thyroid gland that responds poorly to chemotherapy. Surgical removal of all neoplastic tissue is the only potentially curative treatment, while non-surgical treatments show inconsistent results.

Aims: Trailliaedoxa gracilis (WW Smith & Forrest) (TG), a plant of the Rubiaceae family, grows in the province of Sichuan, China.The aims of this study were to examine the effects of TG on morphology, proliferation, viability, and apoptotic rates of medullary thyroid carcinoma cells in vitro.

Methods: Ten fractions and five subfractions of TG were prepared and examined for their effects in one MTC cell line, MTC-SK*). Morphology was studied by electron microscopy: proliferation and viability were quantified by cell counts and WSt-1 cytotoxicity assays. Apoptosis was determined by DAPI staining and luminescent assays for caspases 3/7, 8, 9, 2 and 6.

Results: Five TG-samples were effective: TG-treated MTCSK cells showed a dose-dependent decrease of cell numbers as well as of mitochondrial activity. Furthermore, the TG- fractions activated different caspases, implying that a caspase-dependent apoptotic pathway was involved in this process. In contrast, studies of the same fractions on a normal fibroblast cell line, HF-SAR, showed normal cell growth, and apoptotic activity did not increase. In vivo-investigations and morphologic differentiation-studies are in progress.

Conciusions:The results obtained so far show a potential alternative in antitumor chemotherapy of medullary thyroid carcinoma.

Pfragner R, Hofler H, Behmel A, Ingolic E, Walser V. Establishment and characterization of continuous cell line MTC -SK derived from a human medullary thyroid carcinoma. Cancer Res 50:41604166,1990.