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Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells.

Aguiriano-Moser V, Svejda B, Li ZX, Sturm S, Stuppner H, Ingolic E, Höger H, Siegl V, Meier-Allard N, Sadjak A, Pfragner R - Mol Med Rep (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.

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.

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Antiproliferative effects of Trailliaedoxa gracilis and UA on MTC-SK cells. Cell proliferation was evaluated using a CASY®-1 cell counter and analyzer, and viability was evaluated using a WST-1 assay of MTC-SK cells treated with (A and B) TG-E5-F28 or (C and D) UA for 24, 48 and 72 h. The controls were treated with dimethyl sulfoxide. Data are expressed as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, compared with control. UA, ursolic acid.
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f1-mmr-12-04-5003: Antiproliferative effects of Trailliaedoxa gracilis and UA on MTC-SK cells. Cell proliferation was evaluated using a CASY®-1 cell counter and analyzer, and viability was evaluated using a WST-1 assay of MTC-SK cells treated with (A and B) TG-E5-F28 or (C and D) UA for 24, 48 and 72 h. The controls were treated with dimethyl sulfoxide. Data are expressed as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, compared with control. UA, ursolic acid.

Mentions: The initial screen revealed a reduction in the proliferation of the MTC-SK cells treated with TG-2 (25 μg/ml), according to the CASY®-1 Cell Counter & Analyzer and WST1 results. All the subfractions, which split from TG-2, exhibited significant antiproliferative effects following treatment for 72 h at a concentration of 25 g/ml. TG-E5-18, TG-E5-F19, TG-E5-F23, TG-E5-F41, TG-E5-F43 and TG-E5-F82/A3 exhibited no or little antiproliferative effects; TG-E5-F27 and TG-E5-F44 exhibited low, but significant, antiproliferative effects; and TG-E5-F24, TG-E5-F25, TG-E5-F26, TG-E5-F28 and TG-E5-F42 exhibited marked antiproliferative effects at 10 μg/ml following 72 h incubation. TG-E5-F28 was the subfraction with the highest antiproliferative effects in the MTC-SK cells compared with the MTC-SK cells treated with DMSO (Fig. 1A and B). The activity of several caspases were subsequently analyzed with this subfraction and under transmission electron microscopy. UA also exhibited a dose-dependent antiproliferative effect on the MTC-SK cells compared with those treated with DMSO (Fig. 1C and D).


Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells.

Aguiriano-Moser V, Svejda B, Li ZX, Sturm S, Stuppner H, Ingolic E, Höger H, Siegl V, Meier-Allard N, Sadjak A, Pfragner R - Mol Med Rep (2015)

Antiproliferative effects of Trailliaedoxa gracilis and UA on MTC-SK cells. Cell proliferation was evaluated using a CASY®-1 cell counter and analyzer, and viability was evaluated using a WST-1 assay of MTC-SK cells treated with (A and B) TG-E5-F28 or (C and D) UA for 24, 48 and 72 h. The controls were treated with dimethyl sulfoxide. Data are expressed as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, compared with control. UA, ursolic acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581794&req=5

f1-mmr-12-04-5003: Antiproliferative effects of Trailliaedoxa gracilis and UA on MTC-SK cells. Cell proliferation was evaluated using a CASY®-1 cell counter and analyzer, and viability was evaluated using a WST-1 assay of MTC-SK cells treated with (A and B) TG-E5-F28 or (C and D) UA for 24, 48 and 72 h. The controls were treated with dimethyl sulfoxide. Data are expressed as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, compared with control. UA, ursolic acid.
Mentions: The initial screen revealed a reduction in the proliferation of the MTC-SK cells treated with TG-2 (25 μg/ml), according to the CASY®-1 Cell Counter & Analyzer and WST1 results. All the subfractions, which split from TG-2, exhibited significant antiproliferative effects following treatment for 72 h at a concentration of 25 g/ml. TG-E5-18, TG-E5-F19, TG-E5-F23, TG-E5-F41, TG-E5-F43 and TG-E5-F82/A3 exhibited no or little antiproliferative effects; TG-E5-F27 and TG-E5-F44 exhibited low, but significant, antiproliferative effects; and TG-E5-F24, TG-E5-F25, TG-E5-F26, TG-E5-F28 and TG-E5-F42 exhibited marked antiproliferative effects at 10 μg/ml following 72 h incubation. TG-E5-F28 was the subfraction with the highest antiproliferative effects in the MTC-SK cells compared with the MTC-SK cells treated with DMSO (Fig. 1A and B). The activity of several caspases were subsequently analyzed with this subfraction and under transmission electron microscopy. UA also exhibited a dose-dependent antiproliferative effect on the MTC-SK cells compared with those treated with DMSO (Fig. 1C and D).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.

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.

Show MeSH
Related in: MedlinePlus