Impact of the Operation Ciglitazone on PPAR Activation and Apoptosis Process in Models of Gastrointestinal Cancer in vitro

  • Aldona Katarzyna Olechowska-Jarząb Hospital John Paul 2 in Krakow
  • Aneta Targosz Jagiellonian University
  • Agata Ptak-Belowska Jagiellonian University
Keywords: peroxisome proliferator-activated receptor γ (PPAR-γ), ciglitazone, apoptosis, gastrointestinal cancer



Peroxisome proliferator-activated receptors (PPAR-γ) are nuclear transcription factors which affect the stimulation of glucose and lipid metabolism, modulation of inflammation, tissue sensitivity to insulin, immune response, cell proliferation and differentiation. Current research on PPAR-γ receptors is contradictory.
A significant part of the research suggests that these receptors may be targeted for anti-cancer therapy and have anti-inflammatory properties. Other analyzes speculate on the role of PPAR-γ in promoting cancer. It is therefore important that further studies help to better understand the role of PPAR-γ receptors, which may be relevant in the context of public health and cancer therapy.



The purpose of the study was to determine the effect of ciglitazone (10 μM) on expression of PPAR-γ receptors. In addition, it was investigated whether action on PPAR-γ nuclear receptors with a specific ligand concentration (10 μM of ciglitazone) could lead to increased expression of apoptotic protein (Bcl-2, PKB/Akt) in gastric cancer cells (PANC-1, HT-29) in models In vitro. The effects of ciglitazone were tested in HT-29 and PANC-1 cell lines by MTT growth test (tetrazolium growth assay) for 48 hours post-treatment. Investigation of the relationship between ciglitazone and PPARγ in the context of apoptosis was investigated at the protein level by Western Blot analysis.



The results obtained reflect the trend in the publication. In the conducted studies, it was observed that at 10 and 20 μM concentration of ciglitazone affects the growth of the investigated cell lines (PANC-1, HT-29). In addition, studies have shown that this drug increases the activity of  PPAR-γ receptors and may affect the kinase gene Akt and Bcl-2 through the receptors themselves.


The studies show that treatment of cancer cells 10 μM ciglitazone for a certain time affects the upregulation of anti-apoptotic proteins. What may suggest that certain types of ligand does not result in inhibition of the process of carcinogenesis. Therefore, studies on the effect of PPAR-γ receptors and their ligands on intestinal tumors should be conducted.


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Author Biographies

Aldona Katarzyna Olechowska-Jarząb, Hospital John Paul 2 in Krakow

Department of Physiology Jagiellonian University Medical College, Grzegorzecka 16, 31-
531 Krakow, Poland

Aneta Targosz, Jagiellonian University

Department of Physiology Jagiellonian University Medical College, Grzegorzecka 16, 31-
531 Krakow, Poland

Agata Ptak-Belowska, Jagiellonian University

Department of Physiology Jagiellonian University Medical College, Grzegorzecka 16, 31-
531 Krakow, Poland


1. Debril MB, Renaud JP, Fajas L, The pleiotropic functions of peroxisome proliferators-activated receptor γ. J Mol Med. 2001; 79:30-47.
2. Dubuquoy L, Rousseaux C, Thuru X, PPARγ as a new therapeutic target in infalammatory bowel diseases. Gut 2006; 55:1341–1349.
3. Forman BM, Tontonoz P, Chen J, 15-Deoxy-delta 12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell. 1995; 83:803–812.
4. Fujisawa T, Nakajima A, Fujisawa N, et al. Peroxisome Proliferator-Activated Receptor γ (PPARγ) Suppresses Colonic Epithelial Cell Turnover and Colon Carcinogenesis Through Inhibition of the β-Catenin/T Cell Factor (TCF) Pathway. J. Pharmacol Sci 2008; 106 : 627 – 638.
5. Fröhlich E, Wahl1 R. Chemotherapy and Chemoprevention by Thiazolidinediones. BioMed Research International 2015. Article ID 845340, 14 pages.
6. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000; 405:421-424.
7. Kitamura S. Peroxisome proliferators-acivated receptor γ induces growth arrest and differentiation markers of human colon cancer cells. Jap J Cancer Res. 1999, 90:75-80.
8. Lefebvre AM, Chen I, Desreumaux P, et al. Activation of the peroxisome proliferatoractivated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat Med. 1998; 4:1053–1057.
9. Lehmann JM. An antidiabetic thiazolidinedione is ahigh affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR-γ). J Biol Chem. 1995; 270:12953–6.
10. Malik S, Upadhyaya PK, Miglani S. Thiazolidinediones: a plethro of biological load. International Journal of PharmTech. 2011; 3 (1): 62–75.
11. Marion-Letellier R, De´chelotte P, Iacucci M, et al. Dietary modulation of peroxisome proliferator-activated receptor gamma. Gut 2009; 58: 586-593.
12. Michalik L, Desvergne B, Wahli W. Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat Rev Cancer. 2004; 4:61–70.
13. Murphy GJ, Holder JC. PPAR-γ agonists: therapeutic role in diabetes, inflammation and cancer. TiPS. 2000; 21: 469-474.
14. Ptak-Belowska A, Pawlik MW, Krzysiek-Mączka G, Transcriptional upregulation of gastrin in response to peroxisome proliferator activated receptor gamma agonist triggers cell survival pathways. JPP. 2007; 58 (4): 793–801.
15. Prasad Kota B, Hsun-Wei Huang T, Roufogalis BD. An overview on biological mechanisms of PPARs. Pharmacological Research. 2005; 51:85–94.
16. Rieusset J, Andreelli D, Auboeuf D, Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor γ in human adipocytes. Diabetes. 1999; 49:699-705.
17. Saez E, Tontonoz P, Nelson MC, et al. Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nat Med. 1998; 4:1058–1061.
18. Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes incolon cancer through PPARgamma. Nat Med. 1998; 4:1046–1052.
19. Tyagi S, Gupta P, Singh Saini A, et al. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011; 2(4): 236–240.
20. Wahli W, Braissant O, Desvergne B. Peroxisome proliferator activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more. Chem Biol 1995; 2:261–6.
21. Yang WL, Frucht H. Activation of the PPAR pathway induces apoptosis and COX2 inhibition in HT-29 human colon cancer cells. Carcinogenesis 2001; 22(9): 1379-1383.
How to Cite
Olechowska-Jarząb, A. K., Targosz, A., & Ptak-Belowska, A. (2019). Impact of the Operation Ciglitazone on PPAR Activation and Apoptosis Process in Models of Gastrointestinal Cancer in vitro. EPH - International Journal of Biological & Pharmaceutical Science (ISSN: 2208-2166), 5(2), 01-09. Retrieved from