ArticlePloS one2021
Activated heme synthesis regulates glycolysis and oxidative metabolism in breast and ovarian cancer cells.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes.Veterinary and comparative oncology · 2026Article
- Comprehensive bioinformatics and experimental analysis of PPOX reveals its carcinogenic effect in clear cell renal cell carcinoma.Translational andrology and urology · 2026Article
- Evaluation of Metabolic Characteristics of Cancer Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- 5-Aminolevulinic Acid (5-ALA) Plays an Important Role in the Function of Innate Immune Cells.Inflammation · 2025Article
- Mechanisms of heme transport in the mitochondria.Biochemical Society transactions · 2025Review
- Oncogenic role of fumarate hydratase in breast cancer: metabolic reprogramming and mechanistic insights.Cancer & metabolism · 2025Article
- The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Navigating heme pathways: the breach of heme oxygenase and hemin in breast cancer.Molecular and cellular biochemistry · 2025Review
- LINC01224 promotes the Warburg effect in gastric cancer by activating the miR-486-5p/PI3K axis.In vitro cellular & developmental biology. Animal · 2025Article
- Therapeutic potential of 5-aminolevulinic acid in metabolic disorders: Current insights and future directions.iScience · 2024Review
- Divergent iron regulatory states contribute to heterogeneity in breast cancer aggressiveness.iScience · 2024Article
- Harnessing Porphyrin Accumulation in Liver Cancer: Combining Genomic Data and Drug Targeting.Biomolecules · 2024Article
- A novel mitochondria-related core gene signature to predict the prognosis and evaluate tumour microenvironment in CESC single-cell validation.Journal of cellular and molecular medicine · 2024Article
- Analysis of the potential biological significance of glycosylation in triple-negative breast cancer on patient prognosis.American journal of translational research · 2024Article
- Glucose metabolism reprogramming in gynecologic malignant tumors.Journal of Cancer · 2024Review
- Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Review
- Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023Review
- Research progress on the mechanism of glycolysis in ovarian cancer.Frontiers in immunology · 2023Review
- Oral Microbiome in Nonsmoker Patients with Oral Cavity Squamous Cell Carcinoma, Defined by Metagenomic Shotgun Sequencing.Cancers · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Heme is an essential cofactor for enzymes of the electron transport chain (ETC) and ATP synthesis in mitochondrial oxidative phosphorylation (OXPHOS). Heme also binds to and destabilizes Bach1, a transcription regulator that controls expression of several groups of genes important for glycolysis, ETC, and metastasis of cancer cells. Heme synthesis can thus affect pathways through which cells generate energy and precursors for anabolism. In addition, increased heme synthesis may trigger oxidative stress. Since many cancers are characterized by a high glycolytic rate regardless of oxygen availability, targeting glycolysis, ETC, and OXPHOS have emerged as a potential therapeutic strategy. Here, we report that enhancing heme synthesis through exogenous supplementation of heme precursor 5-aminolevulinic acid (ALA) suppresses oxidative metabolism as well as glycolysis and significantly reduces proliferation of both ovarian and breast cancer cells. ALA supplementation also destabilizes Bach1 and inhibits migration of both cell types. Our data indicate that the underlying mechanisms differ in ovarian and breast cancer cells, but involve destabilization of Bach1, AMPK activation, and induction of oxidative stress. In addition, there appears to be an inverse correlation between the activity of oxidative metabolism and ALA sensitivity. Promoting heme synthesis by ALA supplementation may thus represent a promising new anti-cancer strategy, particularly in cancers that are sensitive to altered redox signaling, or in combination with strategies that target the antioxidant systems or metabolic weaknesses of cancer cells.
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