ArticlePloS one2020
Combining lipoic acid to methylene blue reduces the Warburg effect in CHO cells: From TCA cycle activation to enhancing monoclonal antibody production.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- The role of lactate in retinal health and disease: mechanisms and potential therapeutic strategies. A narrative review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.Antioxidants (Basel, Switzerland) · 2026Review
- Photodynamic Therapy Combined with Anticancer Drug Therapy in the Treatment of Malignant Neoplasms.Cells · 2026Review
- Citric Acid Cycle Genes and Nutrigenetics.International journal of molecular sciences · 2026Review
- Autophagy and Akt-Stimulated Cellular Proliferation Synergistically Improve Antibody Production in CHO Cells.Biotechnology journal · 2024Article
- In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death.International journal of molecular sciences · 2024Article
- Metabolic Shift and Hyperosmolarity Underlie Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2024Review
- Article
- Targeting Mitochondrial Singlet Oxygen Dynamics Offers New Perspectives for Effective Metabolic Therapies of Cancer.Frontiers in oncology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Warburg effect, a hallmark of cancer, has recently been identified as a metabolic limitation of Chinese Hamster Ovary (CHO) cells, the primary platform for the production of monoclonal antibodies (mAb). Metabolic engineering approaches, including genetic modifications and feeding strategies, have been attempted to impose the metabolic prevalence of respiration over aerobic glycolysis. Their main objective lies in decreasing lactate production while improving energy efficiency. Although yielding promising increases in productivity, such strategies require long development phases and alter entangled metabolic pathways which singular roles remain unclear. We propose to apply drugs used for the metabolic therapy of cancer to target the Warburg effect at different levels, on CHO cells. The use of α-lipoic acid, a pyruvate dehydrogenase activator, replenished the Krebs cycle through increased anaplerosis but resulted in mitochondrial saturation. The electron shuttle function of a second drug, methylene blue, enhanced the mitochondrial capacity. It pulled on anaplerotic pathways while reducing stress signals and resulted in a 24% increase of the maximum mAb production. Finally, the combination of both drugs proved to be promising for stimulating Krebs cycle activity and mitochondrial respiration. Therefore, drugs used in metabolic therapy are valuable candidates to understand and improve the metabolic limitations of CHO-based bioproduction.
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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.