scholarly journals Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2

2020 ◽  
pp. 55-55
Author(s):  
Lidija Todorovic ◽  
Gorana Stamenkovic ◽  
Biljana Vucetic-Tadic ◽  
Kazuo Umezawa ◽  
Ana Bozovic ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Drug Treatment ◽  
Cell Line ◽  
Synergistic Effects ◽  
Combined Treatment ◽  
Cancer Cell Line ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Inhibitor Of Apoptosis

The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), Bcell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.

Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines

2007 ◽  
Vol 14 (3) ◽  
pp. 839-845 ◽  
Author(s):  
Maria G Catalano ◽  
Roberta Poli ◽  
Mariateresa Pugliese ◽  
Nicoletta Fortunati ◽  
Giuseppe Boccuzzi
Keyword(s):  
Valproic Acid ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Combined Treatment ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Tubulin Acetylation ◽  
High Doses ◽  
Apoptotic Activity ◽  
Thyroid Cancer Cell Lines

The introduction of paclitaxel into multimodal therapy for anaplastic thyroid carcinoma has failed to improve overall survival. Toxicity rules out the high doses required, especially in older patients. The search for strategies to enhance paclitaxel antineoplastic activity and reduce its side effects is thus advisable. The study aimed to determine whether the histone deacetylase (HDAC) inhibitor valproic acid (VPA) improves the anticancer action of paclitaxel and elucidate the mechanisms underlying the effects of combined treatment. We examined the effect of VPA on the sensitivity to paclitaxel of two anaplastic thyroid carcinoma cell lines (CAL-62 and ARO), and the ability of the drug to determine tubulin acetylation and enhance paclitaxel-induced acetylation. The addition of as little as 0.7 mM VPA to paclitaxel enhances both cytostatic and cytotoxic effects of paclitaxel alone. Increased apoptosis explains the enhancement of the cytotoxic effect. The mechanism underlying this effect is through inhibition of HDAC6 activity, which leads to tubulin hyperacetylation. The results suggest a mechanistic link between HDAC6 inhibition, tubulin acetylation, and the VPA-induced enhancement of paclitaxel effects, and provide the rationale for designing future combination therapies.

scholarly journals Cytokine Production by a New Undifferentiated Human Thyroid Carcinoma Cell Line, FB-11

1997 ◽  
Vol 82 (12) ◽  
pp. 4094-4100
Author(s):  
Lisa Fiore ◽  
Luca E. Pollina ◽  
Gabriella Fontanini ◽  
Rosario Casalone ◽  
Maria T. Berlingieri ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Line ◽  
Messenger Rna ◽  
Thyroid Tissue ◽  
Cancer Cell Line ◽  
In Vitro Study ◽  
Anaplastic Thyroid Cancer ◽  
Human Thyroid ◽  
Immunodeficient Mice

A human anaplastic thyroid cancer cell line FB-1, derived from a 68-yr-old woman who underwent surgery for anaplastic thyroid cancer, has been established. The spindlelike cells have been proliferating stably for more than 2 yr. Karyotype analysis shows many abnormalities and many marker chromosomes have been observed. Heterotransplant of FB-1 cells into severe combined immunodeficient mice has resulted in rapidly growing tumors classified as anaplastic carcinomas, although 50% have shown areas with a trabecular pattern. FB-1 cells failed to express messenger RNA for thyroglobulin; TSH-receptor; thyroperoxidase, and placental angiogenic growth factor. Conversely, PAX8 and thyroid transcription factor 1, whose expression is thyroid specific, was kept in an FB-1 cell line at a level comparable with that observed in normal thyroid tissue. In addition, the present cell line expressed high levels of messenger RNA for high-mobility group proteins (Y) and -C. The in vitro study revealed that FB-1 cells are able to produce high levels of interleukin (IL)-8 and medium amount of IL-6, whereas no release of IL-1-α, IL-1-β, and IL-4 was observed. No modulation of cell proliferation and DNA synthesis in FB-1 cells has been observed after the addition of exogenous IL-6.

scholarly journals In vitro chemoprotective and anticancer activities of propolis in human lymphocytes and breast cancer cells

2015 ◽  
Vol 67 (2) ◽  
pp. 571-581 ◽  
Author(s):  
Olivera Milosevic-Djordjevic ◽  
Darko Grujicic ◽  
Marina Radovic ◽  
Nenad Vukovic ◽  
Jovana Zizic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Combined Treatment ◽  
Cancer Cell Line ◽  
Ethanolic Extracts

Propolis has been used in folk medicine for centuries due to its healing properties. Ethanolic extracts of propolis (EEP) are rich sources of phenolic acid and flavonoids. Natural phenolic compounds may exert chemoprotective activity in cancer cells due to their ability to scavenge free radicals. The aim of this in vitro study was to investigate the genotoxic and anti-mutagenic effects of the EEP on human peripheral blood lymphocytes (PBLs) and their cytotoxic potential on the human breast cancer cell line (MDA-MB-231 cells). Both cell cultures were treated with six concentrations (1, 10, 50, 100, 250 and 500 ?g/ml) of EEP1 and EEP2, separately and in combination with mitomycin C (MMC). Our results show that the EEP1 and EEP2 samples of propolis after separate and combined treatments with MMC did not influence the nuclear division index (NDI). In the combined treatment, both tested EEPs significantly reduced MMC-induced micronuclei (MN) in PBLs. At 48 h after exposure of the MDA-MB-231 cell line to a combined treatment of EEP samples with MMC, the IC50 values were significantly reduced (23.79 and 19.13 ?g/ml, for EEP1+MMC and EEP2+MMC, respectively, in comparison to the single treatment. In conclusion, the tested ethanolic extracts of propolis exhibited a certain level of in vitro antimutagenic activity in PBLs from healthy subjects, and anticancer activity in breast cancer cell line. The presented findings suggest that the ethanolic extracts of propolis show potential in anticancer therapeutic strategy.

scholarly journals Nuclear cysteine cathepsin variants in thyroid carcinoma cells

2010 ◽  
Vol 391 (8) ◽  
Author(s):  
Sofia Tedelind ◽  
Kseniia Poliakova ◽  
Amanda Valeta ◽  
Ruth Hunegnaw ◽  
Eyoel Lemma Yemanaberhan ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Line ◽  
Cathepsin B ◽  
Carcinoma Cell ◽  
Cathepsin L ◽  
Thyroid Stimulating Hormone ◽  
Anaplastic Thyroid Carcinoma ◽  
Biochemical Data ◽  
Thyroid Carcinoma Cell

Abstract The cysteine peptidase cathepsin B is important in thyroid physiology by being involved in thyroid prohormone processing initiated in the follicular lumen and completed in endo-lysosomal compartments. However, cathepsin B has also been localized to the extrafollicular space and is therefore suggested to promote invasiveness and metastasis in thyroid carcinomas through, e.g., ECM degradation. In this study, immunofluorescence and biochemical data from subcellular fractionation revealed that cathepsin B, in its single- and two-chain forms, is localized to endo-lysosomes in the papillary thyroid carcinoma cell line KTC-1 and in the anaplastic thyroid carcinoma cell lines HTh7 and HTh74. This distribution is not affected by thyroid stimulating hormone (TSH) incubation of HTh74, the only cell line that expresses a functional TSH-receptor. Immunofluorescence data disclosed an additional nuclear localization of cathepsin B immunoreactivity. This was supported by biochemical data showing a proteolytically active variant slightly smaller than the cathepsin B proform in nuclear fractions. We also demonstrate that immunoreactions specific for cathepsin V, but not cathepsin L, are localized to the nucleus in HTh74 in peri-nucleolar patterns. As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins.

In Vitro and In Vivo Properties of a Human Anaplastic Thyroid Carcinoma Cell Line Transfected with the Sodium Iodide Symporter Gene

Thyroid ◽  
2004 ◽  
Vol 14 (11) ◽  
pp. 889-895 ◽  
Author(s):  
Yong Jin Lee ◽  
June-Key Chung ◽  
Jae Hoon Shin ◽  
Joo Hyun Kang ◽  
Jae Min Jeong ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Line ◽  
Sodium Iodide ◽  
Carcinoma Cell ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cell Line ◽  
Sodium Iodide Symporter ◽  
Thyroid Carcinoma Cell

scholarly journals Differential effects of natural flavonoids on growth and iodide content in a human Na*/I- symporter-transfected follicular thyroid carcinoma cell line

2004 ◽  
pp. 557-564 ◽  
Author(s):  
JP Schroder-van der Elst ◽  
D van der Heide ◽  
JA Romijn ◽  
JW Smit
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Thyroid Peroxidase ◽  
Thyroid Cancer Cell ◽  
Iodide Uptake ◽  
Iodide Transport

OBJECTIVE: Natural flavonoids (plant pigments) have been shown to inhibit thyroid peroxidase (TPO) in vitro and the growth of thyroid cancer cell lines. We have studied the role of flavonoids on the iodide transport and the growth of the human follicular thyroid cancer cell line (FTC133) which was stably transfected with the human Na(+)/I(-) symporter (hNIS). DESIGN AND METHODS: Cells were treated with flavonoids (0.5-50 microM) for 0, 2, 4 and 6 days; (125)I content and (125)I efflux of the cells and DNA content were measured. RESULTS: Cell growth was inhibited significantly at day 6 by most flavonoids. Eight out of ten flavonoids decreased the (125)I content of the cells at day 4. Morin did not influence the (125)I content of the cells and, surprisingly, myricetin increased the (125)I content of the cells. Kaempferol, apigenin, luteolin and F21388 decreased NIS mRNA expression after 15, 29 and 48 h; after 96 h NIS mRNA returned to normal. CONCLUSION: As TPO is not present in this cell line, the effects of the flavonoids on the iodide uptake are not related to organification. Myricetin was the only flavonoid studied that increased the influx and decreased the efflux of iodide. The effect of myricetin (decreased growth and increased retention of iodide) can be of therapeutic value in the radioiodide treatment of thyroid carcinoma.

New Platinum (II) Ternary Complexes of Formamidine and Pyrophosphate: Synthesis, Characterization and DFT Calculations and In vitro Cytotoxicity

2020 ◽  
Vol 23 (7) ◽  
pp. 611-623
Author(s):  
Ahmed A. Soliman ◽  
Fawzy A. Attaby ◽  
Othman I. Alajrawy ◽  
Azza A.A. Abou-hussein ◽  
Wolfgang Linert
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Theoretical Calculations ◽  
Thermal Analyses ◽  
Cancer Cell Line ◽  
Cellular Growth ◽  
Planar Geometry ◽  
Square Planar ◽  
Vis Spectroscopy

Aim and Objective: Platinum (II) and platinum (IV) of pyrophosphate complexes have been prepared and characterized to discover their potential as antitumor drugs. This study was conducted to prepare and characterize new ternary platinum (II) complexes with formamidine and pyrophosphate as an antitumor candidate. Materials and Methods: The complexes have been characterized by mass, infrared, UV-Vis. spectroscopy, elemental analysis, magnetic susceptibility, thermal analyses, and theoretical calculations. They have been tested for their cytotoxicity, which was carried out using the fastcolorimetric assay for cellular growth and survival against MCF-7 (breast cancer cell line), HCT- 116 (colon carcinoma cell line), and HepG-2 (hepatocellular cancer cell line). Results: All complexes are diamagnetic, and the electronic spectral data displayed the bands due to square planar Pt(II) complexes. The optimized complexes structures (1-4) indicated a distorted square planar geometry where O-Pt-O and N-Pt-N bond angles were 82.04°-96.44°, respectively. Conclusion: The complexes showed noticeable cytotoxicity and are considered as promising antitumor candidates for further applications.

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