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Chemotherapy and chemoprevention by thiazolidinediones.

Fröhlich E, Wahl R - Biomed Res Int (2015)

Bottom Line: Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ).The results of chemopreventive effects of TZDs are also considered.Effects are cell-, species-, and compound-specific and concentration-dependent.

View Article: PubMed Central - PubMed

Affiliation: Internal Medicine, Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Department IV, University of Tuebingen, Otfried-Muellerstrasse 10, 72076 Tuebingen, Germany ; Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, Austria.

ABSTRACT
Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

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Effects of TZDs on apoptosis, migration, invasion, and proliferation of cancer cells and on inflammation. In some ellipses, only one representative is listed; Bax and p53 react similarly, as well as p27 and p21. MMPs represents MMP-2 and MMP-9 and Cyclin E represents cyclin D1, cyclin B1, CDK2, and CDK4. Abbreviations: EGF: epithelial growth factor receptor; PPRE: PPARγ response element, Surv: survivin, E-cad: E-cadherin, b-cat: β-catenin, Cytok: cytokines.
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fig2: Effects of TZDs on apoptosis, migration, invasion, and proliferation of cancer cells and on inflammation. In some ellipses, only one representative is listed; Bax and p53 react similarly, as well as p27 and p21. MMPs represents MMP-2 and MMP-9 and Cyclin E represents cyclin D1, cyclin B1, CDK2, and CDK4. Abbreviations: EGF: epithelial growth factor receptor; PPRE: PPARγ response element, Surv: survivin, E-cad: E-cadherin, b-cat: β-catenin, Cytok: cytokines.

Mentions: PPARγ ligands trigger a conformational change of the PPARγ receptor that attracts transcriptional coactivators of the steroid receptor coactivator family. Once activated by ligand binding, the PPARγ receptor forms heterodimers with the retinoid X-receptor and transcription is initiated. Transcriptional activation may result in decreased proliferation, migration and inflammation and increased differentiation and apoptosis (Figure 2). Inflammatory effects are usually mediated by transrepression [13].


Chemotherapy and chemoprevention by thiazolidinediones.

Fröhlich E, Wahl R - Biomed Res Int (2015)

Effects of TZDs on apoptosis, migration, invasion, and proliferation of cancer cells and on inflammation. In some ellipses, only one representative is listed; Bax and p53 react similarly, as well as p27 and p21. MMPs represents MMP-2 and MMP-9 and Cyclin E represents cyclin D1, cyclin B1, CDK2, and CDK4. Abbreviations: EGF: epithelial growth factor receptor; PPRE: PPARγ response element, Surv: survivin, E-cad: E-cadherin, b-cat: β-catenin, Cytok: cytokines.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383438&req=5

fig2: Effects of TZDs on apoptosis, migration, invasion, and proliferation of cancer cells and on inflammation. In some ellipses, only one representative is listed; Bax and p53 react similarly, as well as p27 and p21. MMPs represents MMP-2 and MMP-9 and Cyclin E represents cyclin D1, cyclin B1, CDK2, and CDK4. Abbreviations: EGF: epithelial growth factor receptor; PPRE: PPARγ response element, Surv: survivin, E-cad: E-cadherin, b-cat: β-catenin, Cytok: cytokines.
Mentions: PPARγ ligands trigger a conformational change of the PPARγ receptor that attracts transcriptional coactivators of the steroid receptor coactivator family. Once activated by ligand binding, the PPARγ receptor forms heterodimers with the retinoid X-receptor and transcription is initiated. Transcriptional activation may result in decreased proliferation, migration and inflammation and increased differentiation and apoptosis (Figure 2). Inflammatory effects are usually mediated by transrepression [13].

Bottom Line: Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ).The results of chemopreventive effects of TZDs are also considered.Effects are cell-, species-, and compound-specific and concentration-dependent.

View Article: PubMed Central - PubMed

Affiliation: Internal Medicine, Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Department IV, University of Tuebingen, Otfried-Muellerstrasse 10, 72076 Tuebingen, Germany ; Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, Austria.

ABSTRACT
Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

Show MeSH
Related in: MedlinePlus