Nonsteroidal Anti-Inflammatory Drugs as PPARγ Agonists Can Induce PRODH/POX-Dependent Apoptosis in Breast Cancer Cells: New Alternative Pathway in NSAID-Induced Apoptosis

Kazberuk, Adam; Chalecka, Magda; Pałka, Jerzy; Surażyński, Arkadiusz

doi:10.3390/ijms23031510

Cited by 12 publications

(9 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the stimulation of PRODH/POX by MET in melanoma cells induced ROS-dependent apoptosis, while PRODH/POX knockout abolished the effect ( Oscilowska et al, 2022 ). A similar effect was found in MCF-7 cells treated with non-steroidal anti-inflammatory drugs ( Kazberuk et al, 2022b ). Other studies on MCF-7 and MDA-MB-231 cells highlighted the role of estrogens and estrogen receptors (ERα and ERβ) in PRODH/POX-dependent apoptosis ( Lewoniewska et al, 2021 ).…”

Section: Discussionsupporting

confidence: 74%

Metformin Induces PRODH/POX-Dependent Apoptosis in Breast Cancer Cells

Huynh

Ościłowska

Szoka

et al. 2022

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

Although the antineoplastic activity of metformin (MET) is well established, the underlying mechanism of the activity is not understood. Since MET activates AMP kinase (AMPK) and proline dehydrogenase/proline oxidase (PRODH/POX) is stimulated by AMPK ligands (implicated in the regulation of cancer cell survival/apoptosis), the effect of MET on PRODH/POX-dependent apoptosis in wild-type MCF-7 cells (MCF-7WT) and POX knockdown MCF-7 cells (MCF-7crPOX cells) was studied. PRODH/POX catalyzes proline degradation generating ROS-induced apoptosis or autophagy. Availability of proline for PRODH/POX functions is regulated by the activity of prolidase (enzyme releasing proline from imidodipeptides), collagen biosynthesis (process consuming proline), and metabolism of proline, ornithine, and glutamic acid. We have found that MET is cytotoxic for MCF-7 cells (IC50∼17 mM), and to the lower extent for MCF-7crPOX cells (IC50∼28 mM). In MCF-7WT cells, the effect was accompanied by the inhibition of DNA biosynthesis, collagen biosynthesis, stimulation of ROS formation, AMPKα phosphorylation, and expression of prolidase, p53, caspase 8, caspase 9, and cleaved PARP. In MET-treated MCF-7crPOX cells, the processes were less affected than in MCF-7WT cells and the expression of caspase 9 was decreased, while cleaved caspase 8 and cleaved PARP were not detected. The effects were accompanied by an increase in the prolidase activity and proline concentration. The mechanism for MET-induced apoptosis involves the up-regulation of prolidase activity and a decrease in collagen biosynthesis contributing to an increase in the concentration of substrate (proline) for PRODH/POX-dependent ROS formation and activation of caspases −9 and −8. The data suggest that PRODH/POX participates in the MET-induced intrinsic and extrinsic apoptosis in MCF-7 cells.

show abstract

Section: Discussionsupporting

confidence: 74%

Metformin Induces PRODH/POX-Dependent Apoptosis in Breast Cancer Cells

Huynh

Ościłowska

Szoka

et al. 2022

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The dysregulated control of inflammation contributes to the initiation, promotion, and metastasis of cancer. Clinical studies have demonstrated that the use of anti-inflammatory drugs displays anti-cancer activity [62][63][64]. The field of tumor immunity is crucial for understanding the dynamics of cancer development, progression, and potential therapeutic interventions (Figure 2).…”

Section: Overview Of Tumor Immunitymentioning

confidence: 99%

An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer

Martinez-Castillo,

M. Elsayed,

López-Berestein

et al. 2023

ncRNA

View full text Add to dashboard Cite

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field with substantial clinical implications.

show abstract

“…The simultaneous activation of PPARγ and RXR has been suggested to promote apoptosis, implicating the upregulation of p53 in breast cancer cell lines [ 215 ]. NSAIDs, considered in cancer prevention due to their inhibitory effect on cyclooxygenases (COX), have recently been proposed to exert their antineoplastic activity through the activation of PPARγ, which induces proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis in breast cancer cells [ 216 ]. In many other studies PPARγ agonists induced apoptosis in bladder cancer [ 217 ], gastric carcinoma [ 133 , 218 ], lung cancer [ 219 ], esophageal adenocarcinoma [ 220 ], pancreatic cancer [ 221 ], hepatocellular carcinoma [ 222 ], neuroblastoma [ 223 ], melanoma [ 141 , 142 ], glioblastoma [ 224 ], leukemia [ 225 ], leiomyoma [ 226 ], mesothelioma [ 153 ], and colon carcinoma [ 227 ].…”

Section: Ppars and Cell Deathmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors and the Hallmarks of Cancer

Wagner

2022

Cells

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) function as nuclear transcription factors upon the binding of physiological or pharmacological ligands and heterodimerization with retinoic X receptors. Physiological ligands include fatty acids and fatty-acid-derived compounds with low specificity for the different PPAR subtypes (alpha, beta/delta, and gamma). For each of the PPAR subtypes, specific pharmacological agonists and antagonists, as well as pan-agonists, are available. In agreement with their natural ligands, PPARs are mainly focused on as targets for the treatment of metabolic syndrome and its associated complications. Nevertheless, many publications are available that implicate PPARs in malignancies. In several instances, they are controversial for very similar models. Thus, to better predict the potential use of PPAR modulators for personalized medicine in therapies against malignancies, it seems necessary and timely to review the three PPARs in relation to the didactic concept of cancer hallmark capabilities. We previously described the functions of PPAR beta/delta with respect to the cancer hallmarks and reviewed the implications of all PPARs in angiogenesis. Thus, the current review updates our knowledge on PPAR beta and the hallmarks of cancer and extends the concept to PPAR alpha and PPAR gamma.

show abstract

Nonsteroidal Anti-Inflammatory Drugs as PPARγ Agonists Can Induce PRODH/POX-Dependent Apoptosis in Breast Cancer Cells: New Alternative Pathway in NSAID-Induced Apoptosis

Cited by 12 publications

References 55 publications

Metformin Induces PRODH/POX-Dependent Apoptosis in Breast Cancer Cells

Metformin Induces PRODH/POX-Dependent Apoptosis in Breast Cancer Cells

An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer

Peroxisome Proliferator-Activated Receptors and the Hallmarks of Cancer

Contact Info

Product

Resources

About