Alteration of PPAR‐GAMMA (PPARG; PPARγ) and PTEN gene expression in acute myeloid leukemia patients and the promising anticancer effects of PPARγ stimulation using pioglitazone on AML cells

• Published in: Molecular genetics & genomic medicine Vol. 9; no. 11; pp. e1818 - n/a
• Main Authors: Esmaeili, Shadi, Salari, Sina, Kaveh, Vahid, Ghaffari, Seyed H., Bashash, Davood
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-11-2021; John Wiley and Sons Inc; Wiley
• Subjects: Acute myeloid leukemia; Anticancer properties; Apoptosis; Cancer; Carrier Proteins; Cell culture; Cell cycle; Flow cytometry; G1 phase; Gene Expression; Humans; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Ligands; Medical research; Myeloid leukemia; Original; Patients; Peroxisome proliferator-activated receptors; peroxisome proliferator‐activated receptor‐γ; Pioglitazone; Pioglitazone - pharmacology; PPAR gamma - genetics; PPARγ; PTEN; PTEN Phosphohydrolase - genetics; PTEN protein; Receptors; Statistical analysis; Statistical methods; Stimulation; Survival; Thermal cycling; U937 Cells; PTEN; peroxisome proliferator-activated receptor-γ; pioglitazone; acute myeloid leukemia; PPARγ
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1818

Background
In the new era of tailored cancer treatment strategies, finding a molecule to regulate a wide range of intracellular functions is valuable. The unique property of nuclear receptor peroxisome proliferator‐activated receptor‐γ (PPARγ; PPARG) in transmitting the anti‐survival signals of the chemotherapeutic drugs has fired the enthusiasm into the application of this receptor in cancer treatment.
Objectives
We aimed to investigate the expression of PPARγ and one of its downstream targets PTEN in non‐M3 acute myeloid leukemia (AML) patients. We also investigated the therapeutic value of PPARγ stimulation using pioglitazone in the AML‐derived U937 cell line.
Methods
The blood samples from 30 patients diagnosed with non‐M3 AML as well as 10 healthy individuals were collected and the mRNA expression levels of PPARγ and PTEN were evaluated. Additionally, we used trypan blue assay, MTT assay, and flow cytometry analysis to evaluate the anti‐leukemic effects of pioglitazone on U937 cells.
Results
While PTEN was significantly downregulated in AML patients as compared to the control group, the expression of PPARγ was increased in the patients’ group. The expression level of PPARγ was also negatively correlated with PTEN; however, it was not statistically significant. Besides, PPARγ stimulation using pioglitazone reduced survival and proliferative capacity of U937 cells through inducing apoptosis and suppression of cell transition from the G1 phase of the cell cycle.
Conclusion
The results of the present study shed more light on the importance of PPARγ and its stimulation in the therapeutic strategies of AML.
The unique property of nuclear receptor peroxisome proliferator‐activated receptor‐γ (PPARγ) in transmitting the anti‐survival signals of the chemotherapeutic drugs has fired the enthusiasm into the application of this receptor in cancer treatment. We found that the expression of PPARγ was increased in non‐M3 AML patients and activation of this receptor using pioglitazone reduced AML cell survival; shedding light on the importance of PPARγ and its ligands in the therapeutic strategies of AML.