lc15-0444 and Thyroid-Neoplasms

lc15-0444 has been researched along with Thyroid-Neoplasms* in 3 studies

Other Studies

3 other study(ies) available for lc15-0444 and Thyroid-Neoplasms

ArticleYear
Gemigliptin, a novel dipeptidyl peptidase-IV inhibitor, exerts a synergistic cytotoxicity with the histone deacetylase inhibitor PXD101 in thyroid carcinoma cells.
    Journal of endocrinological investigation, 2018, Volume: 41, Issue:6

    The influence of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the histone deacetylase inhibitor PXD101 on survival of thyroid carcinoma cells was investigated.. SW1736, TPC-1, 8505C and BCPAP human thyroid carcinoma cells were used. To assess cell survival, cell viability, the percentage of viable cells and dead cells, cytotoxic activity, ATP levels and FACS analysis were measured. To validate the impact of gemigliptin combined with PXD101, the interactions were estimated by obtaining combination index in cells treated with two agents.. In cells treated with gemigliptin or PXD101, cell viability, the percentage of viable cells and ATP levels were reduced, and the percentage of dead cells and cytotoxic activity were elevated. In cells treated with both gemigliptin and PXD101, compared with PXD101 alone, cell death was augmented, and all of the combination index values were lower than 1.0, suggesting the synergism between gemigliptin and PXD101. The percentage of apoptotic cells, and the protein levels of Bcl2 and cleaved poly (ADP-ribose) polymerase were elevated, and the protein levels of xIAP and survivin were reduced. The protein levels of phospho-Akt and phospho-AMPK were elevated, and cell migration was reduced.. Our results demonstrate that gemigliptin induces cytotoxicity in thyroid carcinoma cells. Moreover, gemigliptin has a synergistic activity with PXD101 in the induction of cell death through involvement of Bcl2 family proteins, xIAP and survivin as well as mediation of Akt and AMPK in thyroid carcinoma cells.

    Topics: Apoptosis; Biomarkers, Tumor; Cell Survival; Dipeptidyl-Peptidase IV Inhibitors; Drug Synergism; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Piperidones; Pyrimidines; Signal Transduction; Sulfonamides; Thyroid Neoplasms; Tumor Cells, Cultured

2018
Synergistic cytotoxicity of the dipeptidyl peptidase-IV inhibitor gemigliptin with metformin in thyroid carcinoma cells.
    Endocrine, 2018, Volume: 59, Issue:2

    The influence of the dipeptidyl peptidase-IV inhibitor, gemigliptin alone or in combination with metformin on survival, proliferation, and migration of thyroid carcinoma cells was investigated.. SW1736 and TPC-1 human thyroid carcinoma cells were used.. Gemigliptin and metformin caused cell death in a dose-dependent manner. In cells treated with both gemigliptin and metformin, compared with metformin alone, all of the combination index values were lower than 1.0, suggesting synergistic cytotoxicity of two agents. Cell viability, the percentage of viable cells, ATP levels, and mitochondrial membrane potential decreased; however, cytotoxic activity, and the protein levels of cleaved PARP, phospho-Akt and phospho-AMP-activated protein kinase (AMPK) increased. Administration of wortmannin, but not compound C, further decreased cell viability, and further increased cytotoxic activity. Moreover, compared with control, cell proliferation and migration as well as the protein levels of p53, p21, vascular cell adhesion molecule-1 (VCAM-1), and phospho-extracellular signal-regulated kinase (ERK) 1/2 decreased. The decrement of matrix metalloproteinase-2 and matrix metalloproteinase-9 protein levels was cell specific.. Our results demonstrate that gemigliptin induces cytotoxic activity, and has a synergistic activity with metformin in inducing cytotoxicity via regulation of Akt and AMPK in thyroid carcinoma cells. Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.

    Topics: AMP-Activated Protein Kinases; Cell Death; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Synergism; Humans; Hypoglycemic Agents; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Membrane Potential, Mitochondrial; Metformin; Phosphorylation; Piperidones; Pyrimidines; Signal Transduction; Thyroid Neoplasms; Vascular Cell Adhesion Molecule-1

2018
The dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with NVP-AUY922 has a cytotoxic activity in thyroid carcinoma cells.
    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2017, Volume: 39, Issue:10

    The effect of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the heat shock protein 90 inhibitor NVP-AUY922 (AUY922) on survival of thyroid carcinoma cells was elucidated. The SW1736 and TPC-1 human thyroid carcinoma cells were used. Cell viability, the percentage of viable cells, cytotoxic activity, the percentage of apoptotic cells, and mitochondrial membrane potential were measured. To evaluate the combined effect of gemigliptin with AUY922, the interactions were estimated by calculating combination index. Gemigliptin led to cell death in conjunction with overexpression of the phosphorylated protein levels of Akt, extracellular signal-regulated kinase 1/2, and adenosine monophosphate-activated protein kinase. In gemigliptin-treated cells, wortmannin augmented cell death, whereas AZD6244 and compound C did not affect cell survival. Wortmannin decreased phosphorylated adenosine monophosphate-activated protein kinase protein levels, and AZD6244 increased phosphorylated Akt protein levels. Meanwhile, cotreatment of both gemigliptin and AUY922, compared with treatment of AUY922 alone, potentiated cell death. All the combination index values were lower than 1.0, suggesting synergistic cytotoxicity of gemigliptin with AUY922. In treatment of both gemigliptin and AUY922, compared with AUY922 alone, the protein levels of total and phosphorylated Akt, phosphorylated extracellular signal-regulated kinase 1/2, and phosphorylated adenosine monophosphate-activated protein kinase increased without alteration in those of total extracellular signal-regulated kinase 1/2 and total adenosine monophosphate-activated protein kinase. The percentage of apoptotic cells increased. The protein levels of Bax and cleaved poly (ADP-ribose) polymerase increased, whereas Bcl2 protein levels were unchanged, resulting in increment of Bax/Bcl2 ratio. Transfection of Bax small interfering RNA did not cause any variation in cell viability, the percentage of viable cells and cytotoxic activity. Our results demonstrate that gemigliptin exerts a cytotoxic activity with concomitant alterations in expression of Akt, extracellular signal-regulated kinase 1/2, and adenosine monophosphate-activated protein kinase in thyroid carcinoma cells. Furthermore, gemigliptin synergizes with AUY922 in induction of cytotoxicity via regulation of Akt, extracellular signal-regulated kinase 1/2, and adenosine monophosphate-activated protein kinase as well as involvement of Bcl2 f

    Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma; Cell Line, Tumor; Cell Survival; Dipeptidyl-Peptidase IV Inhibitors; Drug Synergism; Flow Cytometry; Humans; Isoxazoles; Piperidones; Pyrimidines; Resorcinols; Signal Transduction; Thyroid Neoplasms

2017