ArticleInternational journal of molecular sciences2022
Proline Dehydrogenase/Proline Oxidase (PRODH/POX) Is Involved in the Mechanism of Metformin-Induced Apoptosis in C32 Melanoma Cell Line.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Metformin Enhances 2-Aminoethyl Dihydrogen Phosphate-Induced Mitochondrial Dysfunction and Apoptosis in Melanoma Cells.International journal of molecular sciences · 2026Article
- Antitumor Activity of Metformin in Combination with Binimetinib Against Melanoma Cells.International journal of molecular sciences · 2025Article
- Life Factors and Melanoma: From the Macroscopic State to the Molecular Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Comparative in vitro and in silico evaluation of the toxic effects of metformin and/or ascorbic acid, new treatment options in the treatment of Melasma.Toxicology research · 2025Article
- Article
- Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue.Cancers · 2024Article
- Proline Dehydrogenase (PRODH) Is Expressed in Lung Adenocarcinoma and Modulates Cell Survival and 3D Growth by Inducing Cellular Senescence.International journal of molecular sciences · 2024Article
- Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring.Frontiers in oncology · 2024Review
- From Vibrations to Visions: Raman Spectroscopy's Impact on Skin Cancer Diagnostics.Journal of clinical medicine · 2023Review
- The role of mitochondria in the resistance of melanoma to PD-1 inhibitors.Journal of translational medicine · 2023Review
- Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?Frontiers in oncology · 2023Review
- NSAIDs Induce Proline Dehydrogenase/Proline Oxidase-Dependent and Independent Apoptosis in MCF7 Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Metformin Induces PRODH/POX-Dependent Apoptosis in Breast Cancer Cells.Frontiers in molecular biosciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The role of proline dehydrogenase/proline oxidase (PRODH/POX) in the mechanism of antineoplastic activity of metformin (MET) was studied in C32 melanoma cells. PRODH/POX is a mitochondrial enzyme-degrading proline that is implicated in the regulation of cancer cell survival/apoptosis. The enzyme is activated by AMP kinase (AMPK). It has been found that MET induced a significant decrease in cell viability and DNA biosynthesis accompanied by an increase in the expressions of AMPK and PRODH/POX in C32 cells. The mechanism for MET-dependent cytotoxicity on C32 cells was found at the level of PRODH/POX-induced ROS generation and activation of Caspase-3 and Caspase-9 expressions in these cells. The effects were not observed in MET-treated PRODH/POX knock-out C32 cells. Of interest is an MET-dependent increase in the concentration of proline, which is a substrate for PRODH/POX. This phenomenon is due to the MET-dependent inhibition of collagen biosynthesis, which is the main proline-utilizing process. It has been found that the underlying mechanism of anticancer activity of MET involves the activation of AMPK, PRODH/POX, increase in the cytoplasmic concentration of proline, inhibition of collagen biosynthesis, and stimulation of PRODH/POX-dependent ROS generation, which initiate the apoptosis of melanoma cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.